Skip to main content
Wolfson Institute of Population Health - Barts and The London

Projects

Centre for Cancer Prevention

Funding Body:  Cancer Research UK

Principal Investigator:  Dr Sam Smith,

Overview

Use of medications, such as tamoxifen and aspirin, to reduce the risk of cancer is low among eligible patients. Uptake in chemoprevention trials is higher than initiation rates observed in clinical settings. This project will use data from a large nationally representative survey of 1000 GPs to identify potential barriers to prescribing chemoprevention in the NHS.

Centre of Cancer Prevention

Principal Investigator:  Peter Sasieni,

Overview

Often cancer registries in low to middle income countries do not have access to a statistician, while some epidemiologists are unable to use packages such as Nordpred or SEER*Stat that require a high level of technical ability.

This project aims to produce a user-friendly web-based programme for the analysis of cancer incidence data in conjunction with Dr Bray at the International Agency for Research on Cancer (IARC).

There is currently a lack of capacity for supporting registries to analyse their data in a standardised way. This project plans to fill that gap and would be highly beneficial in increasing a registry's ability to analyse and interpret their data for reports and for peer-reviewed research articles.

The software will have one module in basic descriptive statistics (including age-standardised rates, lifetime-risk, population pyramids, and graphs of age-specific rates). A second module for time trends in cancer incidence would include simple graphs (trends with calendar period and birth cohort) as well as options to fit age-period-cohort models and to make both short-term (1-5 years) and medium term (5-20 years) projections.

The projection module will build on the previous work of the two research groups.

Further Information

Relevant methodological problems include:

  • Developing confidence intervals for projections that take into account model uncertainty as well as probabilistic uncertainty
  • Developing random-effects models to perform age-period-cohort modelling in registries that we would anticipate would have similar age-effects and potentially similar trends (period and cohort effects).
  • Integrating the projections of cancer incidence, survival and mortality to ensure that they are consistent

Progress in these areas should enable us to produce better quality-control tools to identify potential artefacts related to registration or other factors.

Centre of Environmental and Preventive Medicine

Principal Investigator:  Graham MacGregor,

Research Group: NDSCR

Overview

Cardiovascular disease including strokes, heart attacks and heart failure, is the leading cause of death and disability worldwide. Raised blood pressure (also called hypertension), is a major cause of cardiovascular disease.

A high salt consumption increases blood pressure.

Although hypertension and cardiovascular disease are not common in children, they originate in childhood.

The current salt intake in children in most countries around the world is very high as it is in adults.

Our project is to determine whether an education programme aimed at primary school children can lower salt intake in children and their families.

The study is being carried out in Changzhi, northern China where salt intake is high.

During the study, we will educate children on how to reduce salt intake. Children will be asked to persuade their families, particularly the person who does the cooking to reduce the amount of salt used during food preparations at home.

If this study is successful, it will lower salt intake in both children and adults.

For adults, this will have an immediate benefit on reducing the risk of suffering a stroke or heart attack.

For children, a lower salt intake may prevent the development of hypertension and cardiovascular disease when they grow older.

Centre for Cancer Prevention

Funding Body:  Cancer Research UK

Principal Investigator:  Professor Peter Sasieni , Professor Rebecca Fitzgerald ,

Overview

Early detection of oesophageal cancer improves outcomes, however the optimal strategy for identifying patients at increased risk from the pre-cancerous lesion Barrett's oesophagus (BE) is not clear.

The BEST3 trial is evaluating whether systematic, non-endoscopic investigation of patients on long-term medication for heartburn and acid reflux symptoms is an effective triage test to increase the diagnosis of BE without unduly burdening the clinical service.

The multi-site cluster-randomised controlled trial will evaluate the ability of the CytospongeTM-TFF3 test to identify BE among patients who do not meet guidelines for urgent referral. The study will aim to recruit over 13,000 patients in 120 practices.

Further Information

The BEST3 study is jointly sponsored by Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge.  If you would like more information, please contact best3trial@qmul.ac.uk

Staff

Beth Muldrew

Laura Baseley

Contact Information

Email: BEST3trial@qmul.ac.uk

Centre of Cancer Prevention

Principal Investigator:  Professor Sue Moss,

Overview

The ongoing European randomised trial of screening for prostate cancer (ERSPC) involves centres in eight countries.

It is one of only two randomised trials worldwide examining the effect of routine screening by PSA testing on mortality from prostate cancer, and has recruited over 160,000 men in the core age-group, 55-69 at entry.

The central database for this study is held in the Centre for Cancer Prevention; data are obtained from all centres at regular intervals, and analyses and reports produced for the Data Monitoring and Scientific Committees.

Staff

  • Professor Sue Moss
  • Mary Neville

Centre for Cancer Prevention

Funding Body:  European Union

Principal Investigator:  Professor Jack Cuzick,

Overview

This multinational study will be conducted in 11 European countries and aims to identify global and local determinants of HPV vaccine acceptability, HPV vaccine uptake and compliance as well as identify logistics and programmatic issues in each country to offer the HPV vaccine, as a potential cervical cancer prevention strategy, to mid-aged women attending screening. 3000 women aged 25-45 years old will be recruited, 25-300 per country. Eligible women will receive a study questionnaire on the HPV vaccine. Women will also be offered the opportunity to receive HPV vaccination.

Professor Cuzick is the National Principal Investigator for the UK and is responsible for the initiation and management of the study, as detailed in the country-specific protocol. In the UK, women will also be asked to perform a self-test for HPV before vaccination and after the final dose. Cervarix for the study will be donated by GlaxoSmithKline.

Centre for Cancer Prevention

Funding Body:  Cancer Research UK

Principal Investigator:  Professor Jack Cuzick,

Overview

The International Breast Cancer Intervention Study 1 (BISI-1) was designed to investigate the use of tamoxifen in preventing breast cancer in women with a higher risk of developing the disease.  Recruitment of women to IBIS-1 ended in March 2011 and it recruited 7,154 women from 36 centres in 9 countries.

A trial of tamoxifen (20mg/d for 5 years) versus placebo in 7,154 women at high risk of breast cancer.  The 10 year results show a 27% reduction in new breast cancers.  The long-term follow up and 20 year results were presented in December 2014 at the San Antonia Breast Cancer Symposium.  The trial was also used to study the impact of tamoxifen on breast density, with first evidence that the response to endocrine therapy is predictable by 12-18% reductions in breast density.

Publications

Cuzick J, Sestak I, Cawthorn S, Hamed H, Holli K, Howell A, Forbes JF ; IBIS-1 Investigators (2015). Tamoxifen for prevention of breast cancer: extended long-term follow-up of the IBIS-I breast cancer prevention trial. Lancet Oncol, 16(1):67-75.

Cuzick J, Forbes JF, Sestak I, Cawthorn S, Hamed H; Holli K, Howell A (2007). Long-Term Results of Tamoxifen Prophylaxis for Breast Cancer – 96-Month Follow-up of the Randomized IBIS-I Trial. JNCI99: 272-282.

Cuzick J, Warwick J, Pinney E, Warren RML, Duffy SW (2004). Tamoxifen and breast density in women at increased risk of breast cancer. J Natl Cancer Inst, 96: 621-628.

Cuzick J, Forbes J, Edwards R, Baum M, Cawthorn S, Coates A, Hamed A, Howell A, Powles T; IBIS Investigators (2002). First results from the International Breast Cancer Intervention Study (IBIS-I): a randomised prevention trial. Lancet, 360: 817-24.

Centre for Cancer Prevention

Funding Body:  Cancer Research UK and ANZ Breast Cancer Trials Group

Principal Investigator:  Professor Jack Cuzick,

Overview

A new trial of extended aromatase inhibitor treatment, metformin and zolendronic acid (bisphophonate) in five year recurrence survivors of ER positive breast cancer at high risk of late recurrence due to being node positive our tumour size >2cm.  

Currently funded for a pilot phase for 300 patients, but the full trial will be a multinational trial of 4,500+ patients.

Centre for Cancer Prevention

Funding Body:  Cancer Research UK, AstraZeneca, Sanofi Aventis

Principal Investigator:  Professor Jack Cuzick,

Overview

IBIS-II DCIS is investigating whether a drug called anastrozole is more effective than tamoxifen, at preventing new cancers, both in the breast affected by ductal carcinoma in-situ (DCIS) and in the opposite (contralateral) breast.

3980 women from 238 centres in 17 countries have enrolled to take part. The trial closed for recruitment in January 2012. Participants are on treatment for 5 years, after which time their health is followed up for a number of years.

IBIS-II Prevention is investigating whether anastrozole can help prevent breast cancer in women who are at high-risk of the disease. The trial recruited 3864 women from 149 centres in 16 countries and it closed for recruitment in January 2012. Participants are on treatment for 5 years, after which time their health is followed up for a number of years.

The first planned analysis were presented at the San Antonio Breast Cancer symposium in December 2013 and in The Lancet.

The results are very positive - participants being treated with anastrozole being 53% less likely to develop breast cancer than those on placebo. There were 40 cases of breast cancer reported in the anastrozole group compared with 85 in the placebo group.

Although women on anastrozole suffered more joint, bone and muscle aches and more hot flushes, these side effects were less than expected in comparison to other research studies on anastrozole and only slightly more common than for women on placebo.

More information can be found on the IBIS-II Website.

 

Centre for Cancer Prevention

Funding Body:  National Institute for Health Research

Principal Investigator:  Professor Sue Moss,

Overview

The NHS breast screening programme (NHSBSP) currently invites women aged 50-70 years for screening by mammography; the age range is being extended to 47-73 years. The original decision to offer screening from age 50 was based on evidence then available from randomised trials which did not show clear evidence of a benefit of screening at younger ages. The AGE trial was uniquely designed to determine the additional benefit of annual mammographic screening from age 40 in reducing deaths from breast cancer.

The trial was conducted in 23 screening units in the UK, and fieldwork was completed in 2005. The first mortality results from the trial did not show a significant reduction in breast cancer deaths in women offered screening. However long term follow up is continuing in order to determine the full effect of this screening on future breast cancer incidence and mortality. This will allow the effect of screening in the trial on breast cancer deaths up to age 60 to be determined, the cost-effectiveness to be compared with that of screening at older ages, and the extent of any over-diagnosis of breast cancer to be estimated.

Centre for Cancer Prevention

Funding Body:  Cancer Research UK

Principal Investigator:  Professor Sue Moss,

Overview

Validated outcome measures are needed to evaluate interventions which aim to improve the early detection of cancer.

The aims of this project are to review data available on interim outcome measures used to evaluate awareness and early detection initiatives for colorectal and ovarian cancers, and to use modelling to study the relationship of short-term and interim outcome measures, and to predict longer-term outcomes, taking into account variation in outcome according to ethnicity and social deprivation.

The application of these findings will enable standardised outcome measures to be used, to aid the comparison of results between studies and the development of effective initiatives.

Centre of Cancer Prevention

Principal Investigator:  Stephen Duffy,

Overview

This work complements our research evaluating service screening. Estimates of the parameters of cancer progression can help to resolve important issues in cancer screening and prevention.

Examples include:

  • How the beneficial and harmful effects of lung cancer screening depend on screening frequency;
  • Individually tailored breast screening intervals based on age, mammographic density, and other risk factors;
  • Risk-stratified endoscopy intervals in patients who have had adenomas removed;
  • Age to begin, interval and age to cease cervical screening taking into account individual level HPV vaccination and introduction of HPV testing;

We will develop simple natural history models of progression of premalignancy to cancer and of subsequent local and distant spread, taking into account potential complexities including: biological heterogeneity (of cancers and of premalignant lesions); host- and lesion-specific covariates influencing progression rates; and factors affecting sensitivity of surveillance.

Our starting point will be Markov processes. Thereafter, to account for these complexities, it will be necessary to include covariates and relax the strong homogeneity assumptions using frailty methods and other approaches.

Centre for Cancer Prevention

Funding Body:  Cancer Research UK

Principal Investigator:  Professor Peter Sasieni,

Overview

The PANTERA study is evaluating the feasibility of aerobic exercise training as a novel primary therapy for men with early prostate cancer. In this randomised control trial (RCT) 50 men undergoing active surveillance for early prostate cancer will be randomised to a complex intervention of aerobic exercise training and behaviour change support for 12 months or to usual care.

The primary outcome will be the feasibility of the intervention including recruitment rate, adherence and attrition due to the intervention, loss to follow-up and adverse event rate. Feasibility outcomes will be assessed using standard methods for rates and proportions. Sample standard deviations of PSA will be obtained, to inform sample size calculations for a full-scale trial.

Further Information

The PANTERA study is sponsored by Sheffield Hallam University.

Centre of Cancer Prevention

Principal Investigator:  Stephen Duffy,

Overview

The Unit is a collaboration of 14 leading scientists from seven institutions, with Professor Stephen Duffy of Queen Mary, University of London as director.

Major areas of activity of the Unit include:

  • Studies of variation in awareness across England and associations with cancer survival
  • Further analysis of the International Cancer Benchmarking Partnership data
  • Quantification of the predictive value of symptoms for cancer
  • Investigation of the relationship between diagnostic intervals and stage of cancer
  • Studies of GP referral habits for suspected cancer
  • Identification of the risk factors for late stage or emergency presentation of cancer
  • Evaluation of the benefits and harms of the national screening programmes for breast, bowel and cervical cancer
  • Identifying barriers to participation in cancer screening and researching policies to improve access and therefore participation
  • Qualitative research on the role of general practice in early diagnosis of cancer

Further Information

The Policy Research Unit in Cancer Awareness, Screening and Early Diagnosis is funded by the Department of Health Policy Research Programme.

The Unit has a five-year programme to research policy issues in the three broad areas of cancer awareness, cancer screening, and early diagnosis of cancer, to inform policies for improving stage at presentation of cancer and thus reducing mortality from the disease.

Staff

Contact

Oley Begum
Email: o.begum@qmul.ac.uk
Phone: +44 (0) 20 7882 5695

Centre for Cancer Prevention

Principal Investigator:  Professor Jack Cuzick,

Overview

This is a series of studies comparing the performance of different HPV and related molecular tests in detecting high grade CIN in a screening or referral context.  

Predictors 1 and 2 looked at approximately 2,000 women referred for abnormal cytology.  

Predictors 3 examined 6,000 residual ThinPrep samples from women attending routine screening.  

Predictors 4 compared collection in ThinPrep versus SurePath in 630 women referred for an abnormal smear. A subset of participants also provided a urine sample for testing. 

Predictors 5 is looking at a range of questions related to self-sampling:

Predictors 5.0 was a preparatory project (60 women) examining the stability of two self-sampling devices under various storage temperature conditions.

Predictors 5.1 is comparing four self-sampling devices plus urine collection in 600 women referred for abnormal cytology.

Publications

Individual detection of 14 high risk human papilloma virus genotypes by the PapType test for the prediction of high grade cervical lesions. J Clin Virol. 2014 Feb 14;60:44-9
Cuzick J, Ho L, Terry G, Kleeman M, Giddings M, Austin J, Cadman L, Ashdown-Barr L, Costa M, Szarewski A.

Comparison of human papillomavirus testing strategies for triage of women referred with low-grade cytological abnormalities. Eur J Cancer. 2013 Jun;49(9):2179-86.
Mesher D, Szarewski A, Cadman L, Austin J, Ashdown-Barr L, Ho L, Terry G, Young M, Stoler M, Bergeron C, McCarthy J, Wright C, Liddle S, Soutter WP, Lyons D, Cuzick J.

Comparing the performance of six human papillomavirus tests in a screening population. Br J Cancer. 2013 Mar 5;108(4):908-13.
Cuzick J, Cadman L, Mesher D, Austin J, Ashdown-Barr L, Ho L, Terry G, Liddle S, Wright C, Lyons D, Szarewski A.

Comparison of seven tests for high grade cervical intraepithelial neoplasia in women with abnormal smears: the Predictors 2 study. J Clin Microbiol. 2012 Jun;50(6):1867-73.
Szarewski A, Mesher D, Cadman L, Austin J, Ashdown-Barr L, Ho L, Terry G, Liddle S, Young M, Stoler M, McCarthy J, Wright C, Bergeron C, Soutter WP, Lyons D, Cuzick J.

Performance of the Abbott RealTime high-risk HPV test in women with abnormal cervical cytology smears. J Med Virol. 2010 Jul;82(7):1186-91.
Cuzick J, Ambroisine L, Cadman L, Austin J, Ho L, Terry G, Liddle S, Dina R, McCarthy J, Buckley H, Bergeron C, Soutter WP, Lyons D, Szarewski A.

Comparison of Predictors for High-Grade Cervical Intraepithelial Neoplasia in Women with Abnormal Smears. Cancer Epidemiol Biomarkers Prev. 2008 Nov;17(11):3033-42.
Szarewski A, Ambroisine L, Cadman L, Austin J, Ho L, Terry G, Liddle S, Dina R, McCarthy J, Buckley H, Bergeron C, Soutter P, Lyons D, Cuzick J.

Performance and Diagnostic Accuracy of a Urine-Based Human Papillomavirus Assay in a Referral Population Cancer Epidemiol Biomarkers Prev 2017;26(7):1053-1059.
Cuzick J, Cadman L, Ahmad A, Ho L, Terry G, Kleeman M, Lyons D, Austin J, Stoler M, Vibat CRT, Dockter J, Robbins D, Billings P, Erlander M.

A comparison of different human papillomavirus tests in PreservCyt versus SurePath in a referral population – PREDICTORS 4 (2016) J Clin Virol 82:145-51.
Cuzick J, Ahmad A, Austin J, Cadman L, Ho L, Terry G, Kleeman M, Ashdown-Barr L, Lyons D, Stoler M, Szarewski A.

Centre for Cancer Prevention

Funding Body:  Barts & The London Charity

Principal Investigator:  Professor Jack Cuzick,

Overview

PROVENT is the first of a series of planned studies to explore minimally toxic treatments to delay or reverse prostate cancer progression in men with clinically localised disease who are being managed conservatively.

This study is a 3x2 trial of placebo versus low dose (100mg) versus standard dose (300mg) aspirin and also vitamin D3 (4,000units/day) versus placebo.

Pilot studies are about to begin and more than 1,000 men are planned to be randomised in the full study in several dozen centres.

A central part of the study is to evaluate markers for progression both at baseline and serially. They include PSA, testosterone, seru, vitamin D levels, urine, PCA3 and the biopsy based CCP score.

Centre for Psychiatry

Principal Investigator:  Kamaldeep Bhui,

Staff

Centre for Cancer Prevention

Principal Investigator:  Professor Jack Cuzick,

Status: active

Overview

Genome-wide association studies (GWAS) have identified a host of new low penetrance genes for a range of cancers.

Our long term goal is to determine their value in breast, prostateand colorectal cancers where we are developing risk assessment tools.  The work is most developed for breast cancer where we already have developed a very widely used risk assessment tool (Tyrer-Cuzick model).

We have found that in our IBIS-1 prevention trial a SNP score adds to conventional factors in the Tyrer-Cuzick model.

Current work is exploring the utility of a SNP score in a routine screening population and determining how best to integrate it into a model containing classical factors and breast density in collaboration with colleagues in Manchester and Sweden.

Further work will expand these approaches to prostate and colorectal cancer.

Centre for Psychiatry

Funding Body:  NIHR rfpb

Principal Investigator:  Kamaldeep Bhui,

Overview

“Forgetfulness” is not uncommon with ageing. It may arise as a normal feature or be a presenting symptom of dementia or depression. While memory problems are not uncommon among older people as a whole, South Asian elders with memory problems often do not access health and social services. Unlike consultations with their GPs for physical health issues, their consultation rates for mental health and memory problems are lower. This leads to reduced access to appropriate services and the under-diagnosis and under-treatment of dementia and depression. This low utilisation of services is of particular concern since the number of elders with dementia is expected to increase significantly in the future.

The overall aim of this research was to improve our understanding of the factors that determine the recognition of and consultation for memory problems among South Asian older people. More specifically, our aims were to:
1) Summarise the current evidence about why South Asian elders may not use their local services and the corresponding factors that determine recognition and consultation for memory problems through conducting a literature review.
2) Adapt an existing tool, the Barts Explanatory Model Inventory Checklist (BEMI-C), to assess explanatory models (EMs) for memory problems in South Asians.
3) Expand our understanding of EMs for the symptoms, causes, consequences and treatments of memory problems prevalent within South Asian communities in the UK – particularly among Indian and Pakistani older people.

This is a cross-sectional study and we used a mixed-methods approach. This included conducting a systematic review of the literature in the first phase of the study, followed by the adaptation of the BEMI-C in the second phase. The adaptation of the BEMI-C was based on the findings from the literature review and qualitative interviews with 25 South Asian participants. The third phase tested the newly developed BEMI-Dementia

(BEMI-D) with 160 younger and older SouthAsians, predominantly Indian and Pakistani, with and without memory problems.

Staff

  • David Challis
  • David Jolley
  • Clarissa Giebel
  • Maria Zubair
  • Angela Worden
  • Kamaldeep Bhui
  • James Nazroo
  • William Pettit
  • Ahmed Lambat
  • Chhaya Kanani
  • Vinay Sudhindra Rao
  • Arun Dey
  • Nitin Purandare
  • DeNDRoN

London Borough of Hackney

Principal Investigator:  Peter Hajek,

Overview

This is a grant to run and evaluate a local specialist smoking cessation service.

Main Contact

Dawn Lindsay
Email: d.lindsay@qmul.ac.uk

Centre of Cancer Prevention

Principal Investigator:  Peter Sasieni,

Overview

Statisticians spend some proportion of their time doing methodological research related to cancer screening.

When screening, one will only identifies disease if it is present and the screen is positive. We will study interval censoring when the sensitivity of the screening test increases as the precancerous lesion grows.

We will apply methods designed for non-compliance to estimate over-diagnosis from trials with extended follow-up in which the control arm are offered screening at the end of the trial.

We will investigate how best to quantify exposure to screening in observational studies.
The issue is whether one can use such studies to accurately estimate the benefit of screening at different intervals.
Various measures will be studied both theoretically and by simulation.

Centre of Cancer Prevention

Principal Investigator:  Peter Sasieni,

Overview

The following problems are being actively studied:

  • Design and analysis of multi-arm clinical trials. There is particular interest in adaptive designs in which arms are dropped.
  • Design and analysis of clinical trials with factorial designs to study multiple interventions in a single trial.
  • Analysis of clinical trials subject to non-compliance and unplanned cross-over.
  • Design of predictive biomarker trials to detect a qualitative interaction.

Health and Lifestyle Research Unit

Principal Investigator:  Professor Peter Hajek ,

Overview

If you are interested in taking part please call: 0207 882 5722 (lines are open Monday-Friday, 9-5pm)
Or click the link to email us: health-research@qmul.ac.uk

This study is approved by the National Research Ethics Committee West Midlands.

Thank you for your interest in this new study looking to follow-up people who both smoke and vape (i.e. 'dual users'), to learn about how this use develops and what proportion of nicotine such ‘dual users’ get from vaping and from smoking over time. This study is the first of its kind, and your participation could make a difference to our understanding of e-cigarettes and their use.

The study is run by the Health and Lifestyle Research Unit at the Wolfson Institute of Preventive Medicine, Queen Mary University of London, a world leader in this field. If you decide to take part, we will ask you to complete some questionnaires over the phone and provide a saliva sample by post at baseline and again at 3 and 6 and 12 months.

In addition to this, if you are interested in receiving help to stop smoking altogether, we will provide you with stop-smoking medication and telephone support.

Further details can be found on this Information Sheet [PDF 102KB]

Centre for Cancer Prevention

Funding Body:  Cancer Research UK, AstraZeneca

Principal Investigator:  Professor Jack Cuzick,

Overview

Long-term Anastrozole vs. Tamoxifen Treatment Effects (LATTE) is the post ten-year follow up study of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) adjuvant trial in postmenopausal women with early breast cancer.

The ATAC trial was a 10 year study designed to compare the efficacy and safety of Anastrozole and Tamoxifen Alone or in Combination, as treatment in post-menopausal women with invasive breast cancer.  There were approximately 9,500 patients included in the trial who received one of the following treatments for 5 years, and then off treatment for the remaining 5 years:

  • Anastrozole + Tamoxifen placebo
  • Tamoxifen + Anastrozole placebo
  • Anastrozole + Tamoxifen

Study Design

LATTE is the long-term follow-up study from the ATAC trial which occured over 10 years ago.  It includes approximately 4,300 post-menopausal women with breast cancer who were randomised to receive either Anastrozole + Tamoxifen placebo or Tamoxifen + Anastrozole placebo in the ATAC trial.

LATTE aims to provide additional efficacy data on breast cancer recurrence, information on survival, new primary cancers, major ischaemic cardiac and cerebrovascular events.

Treatments

There are no trial drugs or treatments associated with this observational study.

Objectives

To compare the ATAC patients randomised to receive Anastrozole to those randomised to receive Tamoxifen (and who have now all completed 5 years on trial therapy followed by 5 years off trial therapy).

Primary Objectives

  • Time to recurrence of breast cancer in the post 10 year period (defined as the earliest of local or distant recurrence, new primary breast cancer, or death)
  • Death after recurrence
Secondary Objectives
  • Cancer-specific survival
  • New breast primaries
  • Other cancers
  • Ischaemic cardiac and cerebrovascular events
  • Hip (and other) fractures

Inclusion Criteria

  • Post-menopausal women with breast cancer who were randomised to receive the mono-therapy arm (Anastrozole or Tamoxifen) in the ATAC trial
  • Not known to have died and alive after 10 years ATAC follow-up
  • Did not withdraw consent in the ATAC trial

Data Processing & Patient Confidentiality

Currently, sites choose to collect follow-up data using a variety of methods determined by local practice, aiming to do so on an annual basis. These include:

  • Routine clinic visit, based on local practice
  • By requesting information from GPs
  • Where appropriate, by post or telephone
  • From Hospital Tracking System

Queen Mary University of London will also collect information about LATTE study participants from NHS Digital, as well as other devolved public health bodies. This information will include participant name, date of birth, NHS number, and post code and health information, which is regarded as a special category of information. We will use these data to help assess the effectiveness of the trials’ interventions.

As Data Controller, Queen Mary University of London (QMUL) is responsible for the collection, storage and processing of these data for the study. These data include the following identifiable data, categorised under the General Data Protection Regulation (GDPR) as personal and sensitive:

  • Cancer incidence (any diagnosis of cancer and the type of cancer it is);;
  • Mortality data (in the event of death we will receive information confirming the date and cause of death);
  • Hospital Episode Statistics (HES) which utilises your in-patient, out-patient and A&E data (to look for other significant clinical events of interest to the clinical trial e.g. serious fractures, heart attacks);

The level of data collected from NHS/public health bodies will only be identifiable to us at QMUL and will not be shared with any third parties. Only authorised staff at the LATTE Coordinating Centre are able to access the data and only for specific purposes related to the trial. The data is stored in a secure, restricted-access environment. The data will be retained until destruction at the end of the study archiving period, which will be in 2039.

The legal bases for processing this data are exemption from Section 251 of the NHS Act 2006, as well as Article 6(1)(e) ‘performance of a task carried out in the public interest’ and Article 9(2)(j) ‘public interest, scientific or historical research purposes or statistical purposes’ pursuant to the GDPR.

As a University we use personally-identifiable information to conduct research to improve health, care and services. As a publicly-funded organisation, we have to ensure that it is in the public interest when we use personally-identifiable information from people who have agreed to take part in research. This means that when you agree to take part in a research study, we will use your data in the ways needed to conduct and analyse the research study. Your rights to access, change or move your information are limited, as we need to manage your information in specific ways in order for the research to be reliable and accurate. If you withdraw from the study, we will keep the information about you that we have already obtained. To safeguard your rights, we will use the minimum personally-identifiable information possible.

Health and care research should serve the public interest, which means that we have to demonstrate that our research serves the interests of society as a whole. We do this by following the UK Policy Framework for Health and Social Care Research.

If you wish to raise a complaint on how we have handled your personal data, you can contact our Data Protection Officer (data-protection@qmul.ac.uk) who will investigate the matter. If you are not satisfied with our response or believe we are processing your personal data in a way that is not lawful you can complain to the Information Commissioner’s Office (ICO).

Should you have any further questions about the study, please contact the LATTE Central Coordinating Office for more detail on how to withdraw from further data collection as part of the LATTE study, by calling 020 7882 5973, e-mailing latte@qmul.ac.uk or contacting their LATTE study site.

Additional Information

Arimidex, Tamoxifen, Alone or in Combination (ATAC) Trialists' Group, Forbes JF, Cuzick J, Buzdar A, Howell A, Tobias JS, Baum M (2008). Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial. Lancet Oncol., 9(1):45-53.

 

The ATAC Trialists' Group (2003) (includes J Cuzick, Independent Statistician). Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early-stage breast cancer - Results of the ATAC (arimidex, tamoxifen alone or in combination) trial efficacy and safety update analysis. Cancer, 98: 1802-1810.

 

The ATAC Trialists' Group: Buzdar A, Howell A, Cuzick J, Wale C, Distler W, Hoctin-Boes G, Houghton J, Locker GY, Nabholtz JM (2006). Comprehensive side-effect profile of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: long-term safety analysis of the ATAC trial. Lancet Oncol. Aug; 7(8):633-43.

 

Baum M, Budzar AU, Cuzick J, et al (2002). Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial. Lancet, 359: 2131-2139.

 

Cuzick, J. (2015). Statistical controversies in clinical research: long-term follow-up of clinical trials in cancer. Annals of Oncology26(12), 2363–2366. http://doi.org/10.1093/annonc/mdv392

 

Cuzick J, Sestak I, Cella D, Fallowfield L; on behalf of the ATAC Trialists' Group (2008). Treatment-emergent endocrine symptoms and the risk of breast cancer recurrence: a retrospective analysis of the ATAC trial. Lancet Oncol., 9(12):1143-1148.

 

Cuzick J, Sestak I, Baum M, Buzdar A, Howell A, Dowsett M, Forbes JF, on behalf of the ATAC/LATTE investigators (2010). Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 10-year analysis of the ATAC trial. Lancet Onc., 11(12):1109-10.

  

Cuzick, J., M. Dowsett, S. Pineda, C. Wale, J. Salter, E. Quinn, L. Zabaglo, E. Mallon, A. R. Green, I. O. Ellis, A. Howell, A. U. Buzdar and J. F. Forbes (2011). Prognostic Value of a Combined Estrogen Receptor, Progesterone Receptor, Ki-67, and Human Epidermal Growth Factor Receptor 2 Immunohistochemical Score and Comparison With the Genomic Health Recurrence Score in Early Breast Cancer. Journal of Clinical Oncology 29(32): 4273-4278.

 

Eastell R, Adams J, Clack G, Howell A, Cuzick J, Mackey J, Beckmann MW, Coleman RE (2011). Long-term effects of anastrozole on bone mineral density: 7-year results from the ATAC trial. Ann Oncol. 2011 Apr;22(4):857-62

 

Eastell R, Adams JE, Coleman RE, Howell A, Hannon RA, Cuzick J, Mackey JR, Beckmann MW, Clack G (2008). Effect of anastrozole on bone mineral density: 5-year results from the anastrozole, tamoxifen, alone or in combination trial 18233230. J Clin Oncol, 26(7):1051-7.

 

Eastell R, Hannon R, Cuzick J, Dowsett M, Clack G, Adams J (2006) on behalf of ATAC Trialists Group. Effect of an Aromatase Inhibitor on BMD and Bone Turnover Markers: 2-year Results of the Anastrozole, Tamoxifen, Alone or in Combination (ATAC) Trial. Journal of Bone and Mineral Research, Vol 21:8, 1215-1223.

 

Gnant, M., I. Sestak, M. Filipits, M. Dowsett, M. Balic, E. Lopez-Knowles, R. Greil, P. Dubsky, H. Stoeger, M. Rudas, R. Jakesz, S. Ferree, J. W. Cowens, T. Nielsen, C. Schaper, C. Fesl and J. Cuzick (2015). Identifying clinically relevant prognostic subgroups of postmenopausal women with node-positive hormone receptor-positive early-stage breast cancer treated with endocrine therapy: a combined analysis of ABCSG-8 and ATAC using the PAM50 risk of recurrence score and intrinsic subtype. Ann Oncol 26(8): 1685-1691.

 

Howell A, Cuzick J, Baum M, Buzdar A, Dowsett M, Forbes JF, Hoctin-Boes G, Houghton J, Locker GY, Tobias JS; ATAC Trialists' Group (2005). Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years' adjuvant treatment for breast cancer. Lancet, 365: 60-2. (Correspondence, Lancet, 365: 1225-1226).

Sestak I, Cuzick J, Dowsett M, Lopez-Knowles E, Filipits M, Dubsky P, et al.(2015) Prediction of Late Distant Recurrence After 5 Years of Endocrine Treatment: A Combined Analysis of Patients From the Austrian Breast and Colorectal Cancer Study Group 8 and Arimidex, Tamoxifen Alone or in Combination Randomized Trials Using the PAM50 Risk of Recurrence Score. J Clin Oncol., 33(8):916-22. 

Sestak I, Sapunar F, Cuzick J (2009). Aromatase inhibitor-induced carpal tunnel syndrome: results from the ATAC trial. J Clin Oncol., 27(30):4961-5.

Health and Lifestyle Research Unit

Principal Investigator:  Project Investigator: Dr Dunja Przulj,

If you are interested in taking part please call: 0207 882 5722 (lines are open Monday-Friday, 9-5pm)

Or click the link to email us: health-research@qmul.ac.uk


Thank you for your interest in this new study looking at how much nicotine people obtain from different types/brands of e-cigarettes and other alternative nicotine delivery devices such as ‘heat not burn’ products.

The study is run by the Health and Lifestyle Research Unit at Wolfson Institute of Preventive Medicine, Queen Mary University of London.

 

If you decide to take part, we will ask you to come into our clinic at Stepney Green for morning sessions after not smoking or vaping for at least 12 hours. These sessions will take place on 4-5 separate occasions, lasting around 45 – 60 minutes. Within these times you will be given the opportunity to test different e-cigarette or alternative nicotine delivery devices.

 

Please note these sessions will involve blood sampling. 14 blood samples will be drawn over a 30 minute period.

 

You will receive compensation for your time and travel expenses at the end of each session.


Further details can be found on this (Participant information sheet [PDF 156KB])

If you are interested in taking part please call: 0207 882 5722 (lines are open Monday-Friday, 9-5pm), or click the link to email us: health-research@qmul.ac.uk

 

This study is approved by Queen Mary University of London’s Ethics of Research Committee (QMERC2018/09).

Centre for Cancer Prevention

Funding Body:  Memorial Sloan Kettering Cancer Centre, SPORE, CRUK

Principal Investigator:  Professor Jack Cuzick,

Overview

Prognostic Factors in Prostate Cancer for Patients Treated by Watchful Waiting, conducted by the Transatlantic Prostate Group (TAPG) is a long-term retrospective epidemiology cohort study on factors predicting clinical progression of prostate cancer.

Study Design

The TAPG study is the long-term follow-up that started in 1999. It comprises approximately 3,300 men diagnosed with prostate cancer between 1990 and 2006. This exploratory study aims to identify prognostic markers that will more accurately predict the probability of recurrence and allow for better patient selection for radical treatment of prostate cancer.

There is no direct patient involvement as this is a retrospective study carried out in patients registered on UK regional cancer databases, as having prostate cancer diagnosed between 1990 and 2006 inclusively.

Hospital sites participating in the TAPG study send pathology tissue biopsy slides and blocks to the Central Coordinating Team at the Centre for Cancer Prevention. These slides and blocks are analysed by the study reference pathologist and undergo biomarker testing to determine what factors can better predict clinical progression of prostate cancer. At the end of the study, the slides and blocks will be returned to the originating hospital sites.

National cancer registries or health information centres such as the Scottish Cancer registry, Public Health England and NHS Digital provide the Central Coordinating team with follow-up information on the patients included in the study.

There are no trial drugs or treatments associated with this observational study.

Objectives

In men diagnosed with prostate cancer and treated by radical prostatectomy or watchful waiting, the standard clinical factors (such as Prostate Specific Antigens (PSA), clinical stage, and Gleason Grade) have been shown to predict the probability of recurrence with modest accuracy. The TAPG study aims to develop a prognostic model for the prediction of death from prostate cancer after conservative treatment of prostate cancer using standard factors (PSA, clinical grade, Gleason grade). Secondly, it aims to determine whether prediction of disease recurrence can be improved by the addition of other pathological, biological or molecular markers to the standard clinical factors.

The data collected as part of the TAPG study will help assess the effectiveness of the interventions that prostate cancer patients receive and will substantially aid the decision-making process for the treatment of early prostate cancer, allowing better patient selection for radical therapy.


Inclusion Criteria

The main inclusion criteria includes:

  • Patients diagnosed with prostate cancer aged 18-76 at the time of diagnosis.
  • Patients must have had a baseline serum PSA level measured before starting any treatment and within six months of diagnosis
  • Patients must have been diagnosed between 1990 and 2006 with a clinically localized prostate cancer

Patient Confidentiality

Queen Mary University of London will also collect information about TAPG study participants from NHS Digital, as well as other devolved public health bodies. This information will include participant name, date of birth, NHS number, and post code and health information, which is regarded as a special category of information. We will use these data to help assess the effectiveness of the trials’ interventions.

As Data Controller, Queen Mary University of London (QMUL) is responsible for the collection, storage and processing of these data for the study. These data include the following identifiable data, categorised under the General Data Protection Regulation (GDPR) as personal and sensitive:

  1. Cancer incidence (any diagnosis of cancer and the type of cancer it is)
  2. Mortality Data (in the event of death we will receive information confirming the date and cause of death)

The level of data collected from NHS/public health bodies will only be identifiable to us at QMUL and will not be shared with any third parties. Only authorised staff at the TAPG Coordinating Centre are able to access the data and only for specific purposes related to the trial. The data is stored in a secure, restricted-access environment. The data will be retained until destruction at the end of the study archiving period, which will be in 2050.

The legal bases for processing this data are exemption from Section 251 of the NHS Act 2006, as well as Article 6(1)(e) ‘performance of a task carried out in the public interest’ and Article 9(2)(j) ‘public interest, scientific or historical research purposes or statistical purposes’ pursuant to the GDPR.

As a University we use personally-identifiable information to conduct research to improve health, care and services. As a publicly-funded organisation, we have to ensure that it is in the public interest when we use personally-identifiable information from people who have agreed to take part in research. This means that when you agree to take part in a research study, we will use your data in the ways needed to conduct and analyse the research study. Your rights to access, change or move your information are limited, as we need to manage your information in specific ways in order for the research to be reliable and accurate. If you withdraw from the study, we will keep the information about you that we have already obtained. To safeguard your rights, we will use the minimum personally-identifiable information possible.

Health and care research should serve the public interest, which means that we have to demonstrate that our research serves the interests of society as a whole. We do this by following the UK Policy Framework for Health and Social Care Research.

If you wish to raise a complaint on how we have handled your personal data, you can contact our Data Protection Officer (data-protection@qmul.ac.uk) who will investigate the matter. If you are not satisfied with our response or believe we are processing your personal data in a way that is not lawful you can complain to the Information Commissioner’s Office (ICO).

 If you would like any further information about the TAPG epidemiological study, please contact the TAPG Central Coordinating Office by telephone 020 7882 5973 or by e-mail tapg@qmul.ac.uk.   

 

Additional Information

Ahmad AS, Vasiljević N, Carter P, et al. A novel DNA methylation score accurately predicts death from prostate cancer in men with low to intermediate clinical risk factors. Oncotarget. 2016;7(44):71833-71840. doi:10.18632/oncotarget.12377.

 

Attard G, Clark J, Ambroisine L, et al. Heterogeneity and clinical significance of ETV1 translocations in human prostate cancer. British Journal of Cancer. 2008;99(2):314-320. doi:10.1038/sj.bjc.6604472.

 

Berney DM, Gopalan A, Kudahetti S, et al. Ki-67 and outcome in clinically localised prostate cancer: analysis of conservatively treated prostate cancer patients from the Trans-Atlantic Prostate Group study. British Journal of Cancer. 2009;100(6):888-893. doi:10.1038/sj.bjc.6604951.

 

Berney DM, Fisher G, Kattan MW, et al. Major shifts in the treatment and prognosis of prostate cancer due to changes in pathological diagnosis and grading. BJU international. 2007;100(6):1240-1244. www.summon.com. doi: 10.1111/j.1464-410X.2007.07199.x.

 

Cuzick J, Stone S, Fisher G, et al. Validation of an RNA cell cycle progression score for predicting death from prostate cancer in a conservatively managed needle biopsy cohort. British Journal of Cancer. 2015;113(3):382-389. doi:10.1038/bjc.2015.223.

 

Cuzick J, Yang ZH, Fisher G, et al. Prognostic value of PTEN loss in men with conservatively managed localised prostate cancer. British Journal of Cancer. 2013;108(12):2582-2589. doi:10.1038/bjc.2013.248.

 

Cuzick J, Berney DM, Fisher G, et al. Prognostic value of a cell cycle progression signature for prostate cancer death in a conservatively managed needle biopsy cohort. British Journal of Cancer. 2012;106(6):1095-1099. doi:10.1038/bjc.2012.39.

 

Cuzick J, Swanson GP, Fisher G, et al. Prognostic value of an RNA expression signature derived from cell cycle proliferation genes for recurrence and death from prostate cancer: A retrospective study in two cohorts. The lancet oncology. 2011;12(3):245-255. doi:10.1016/S1470-2045(10)70295-3.

 

Cuzick J, Fisher G, Kattan MW, et al. Long-term outcome among men with conservatively treated localised prostate cancer. British Journal of Cancer. 2006;95(9):1186-1194. doi:10.1038/sj.bjc.6603411.

 

Fisher G, Yang ZH, Kudahetti S, et al. Prognostic value of Ki-67 for prostate cancer death in a conservatively managed cohort. British Journal of Cancer. 2013;108(2):271-277. doi:10.1038/bjc.2012.598.

 

Reid AHM, Attard G, Ambroisine L, et al. Molecular characterisation of ERG, ETV1 and PTEN gene loci identifies patients at low and high risk of death from prostate cancer. British Journal of Cancer. 2010;102(4):678-684. doi:10.1038/sj.bjc.6605554.

Health and Lifestyle Research Unit

Principal Investigator:  Professor Peter Hajek,

Overview

If you are interested in taking part please call: 0207 882 5722 (lines are open Monday-Friday, 9-5pm)
Or click the link to email us: health-research@qmul.ac.uk

Thank you for your interest in this new study looking to follow up people who both smoke and vape, to learn about how this ‘dual use’ develops over time. This study is one of the first of its kind, and your participation could make a difference to our understanding of e-cigarettes and their use.

The study is run by the Health and Lifestyle Research Unit at Wolfson Institute of Preventive Medicine, Queen Mary University of London.

If you decide to take part, we will ask you to fill in a questionnaire (either online or by post) when you join the study and again 3, 6, 9 and 12 months later.


Further details can be found on this Participant Information Sheet [PDF 262KB].

If you are interested in taking part please call: 0207 882 5722 (lines are open Monday-Friday, 9-5pm)
Or click the link to email us: health-research@qmul.ac.uk

 

This study is approved by Queen Mary University of London’s Ethics of Research Committee (QMREC2017/41).

Centre for Psychiatry

Principal Investigator:  Kamaldeep Bhui,

 
Ductal carcinoma in situ (DCIS) is described as a very early form of breast cancer, where cancer cells are present in milk ducts, but have not spread to the surrounding breast tissue. It is estimated that approximately a fifth of all screen-detected breast cancers are DCIS, with around 4,800 people diagnosed with DCIS in the UK each year.
 
Lead author Professor Jack Cuzick from QMUL said:
“We found that anastrozole and tamoxifen had similar overall efficacies, with slightly better outcomes for those who took anastrozole. But more importantly, because of their very different side-effects, anastrozole can be offered as an alternative for patients who may not tolerate tamoxifen as well or have previous illnesses making tamoxifen unsuitable.
“Now we know that anastrozole is effective for treating hormone sensitive ductal carcinoma in situ, women will have a greater choice of treatments to suit their own previous medical histories and tolerability of medications.”
The research was funded by Cancer Research UK, and the results are being presented at the 2015 San Antonio Breast Cancer Symposium on 11th November and published in The Lancet.
 
Professor Peter Johnson, Cancer Research UK’s chief clinician, said:
“Breast cancer is the single most common cancer in the UK and we continue to learn more about how to prevent and treat it through our research. We already know that tamoxifen can reduce the risk of cancer developing in some women who have early changes in the breast, but some get unacceptable side effects.This trial shows that there is an equally good alternative in anastrozole, which may suit some people better. It’s important we continue to gain more insight into the side effects of different drugs and understand who is at higher risk and who is most likely to benefit."
The study looked at 2,980 postmenopausal women with DCIS in 14 countries, who were either given anastrozole or tamoxifen for five years after surgery. After a median follow-up of 7.2 years, 144 participants developed breast cancer, and 69 died, of which four were due to breast cancer.
 
The groups had a similar number of cases of the disease recurring, whether they took tamoxifen or anastrozole. Those who took anastrozole had an 11 per cent lower rate of recurrence of DCIS or invasive cancer than those who took tamoxifen, but this difference was not significant.
 
The women in the two groups had different side effects. Women who took anastrozole experienced fewer womb and ovarian cancers and non melanoma skin cancers, and fewer deep vein thromboses and gynecological issues, compared with those who took tamoxifen. However, more strokes, fractures and musculoskeletal issues were seen among those receiving anastrozole.
 
The trial was limited by its lower-than-expected event rate, which adds uncertainly about the lack of statistical significance of some of the small differences seen. The authors say it is too early to assess the effect of these treatments on mortality, and long-term follow-up and further research is planned to study these issues.
 
The study was also funded by National Health and Medical Research Council Australia, Breast Cancer Research Fund, and AstraZeneca.
 
Following on from IBIS-II, the IBIS 3 Feasibility study will begin recruitment in 18 UK sites in January 2016, with the aim of comparing further treatments for 300 breast cancer survivors at high risk of late recurrence.
 

Publication

 
John F Forbes, Ivana Sestak, Anthony Howell, Bernardo Bonanni, Nigel Bundred, Christelle Levy, Gunter von Minckwitz, Wolfgang Eiermann, Patrick Neven, Michael Stierer, Chris Holcombe, Robert E Coleman, Louise Jones, Ian Ellis, Jack Cuzick, on behalf of the IBIS-II investigators.
The Lancet. 11 December 2015.

For Media Information contaact:

 
Joel Winston
Public Relations Manager (School of Medicine and Dentistry)
Queen Mary University of London
Tel: +44 (0)20 7882 7943 / +44 (0)7970 096 188

Dr Erminia Colucci from the Wolfson Institute of Preventive Medicine recently won the Andrej Marusic Award. 
The award is an acknowledgement of contribution to suicide research and prevention by young scholars and is awarded by the International Association for Suicide Prevention (IASP). 
It honours the life of Slovenian psychiatrist Andrej Marusic (1965-2008) who made major scientific contributions to suicidology. 
Dr Colucci said: “The IASP is the key international organisation in the field and I am honoured to be the winner of the award.”

Please follow this link for the profile of Dr Erminia Colucci

Please click here for more information about Andrej Marusic Award

Centre for Cancer Prevention

Principal Investigator:  Professor Jack Cuzick,

Overview

Biomarker study of most UK patients in the ATAC trial.

A range of IHC, FISH and expression profile marker panels have been studied. Combination of IHC for ER, PgR, ki67 and FISH for Her2 used to create IHC4 panel. Several expression profile panels evaluated including Oncotype, Pam50 (Prosigna) and, BCI.

Our current focus is on markers for late recurrence. Original blocks being recollected for further studies.

Publications

Prediction of late distant recurrence in patients with oestrogen-receptor-positive breast cancer: a prospective comparison of the breast- cancer index (BCI) assay, 21-gene recurrence score, and IHC4 in the TransATAC study population. Lancet Oncol. 2013 Oct;14(11):1067-76.
Sgroi DC, Sestak I, Cuzick J, Zhang Y, Schnabel CA, Schroeder B, Erlander MG, Dunbier A, Sidhu K, Lopez-Knowles E, Goss PE, Dowsett M.

Immunohistochemical BAG1 expression improves the estimation of residual risk by IHC4 in postmenopausal patients treated with anastrazole or tamoxifen: a TransATAC study. Breast Cancer Res Treat. 2013 Jul;140(2):253-62.
Afentakis M, Dowsett M, Sestak I, Salter J, Howell T, Buzdar A, Forbes J, Cuzick J.

Factors Predicting Late Recurrence for Estrogen Receptor-Positive Breast Cancer. J Natl Cancer Inst. 2013 Oct 2;105(19):1504-11.
Sestak I, Dowsett M, Zabaglo L, Lopez-Knowles E, Ferree S, Cowens JW, Cuzick J.

Comparison of PAM50 Risk of Recurrence Score With Oncotype DX and IHC4 for Predicting Risk of Distant Recurrence After Endocrine Therapy. J Clin Oncol. 2013 Aug 1;31(22):2783-90.
Dowsett M, Sestak I, Lopez-Knowles E, Sidhu K, Dunbier AK, Cowens JW, Ferree S, Storhoff J, Schaper C, Cuzick J.

Effects of cyclin D1 gene amplification and protein expression on time to recurrence in postmenopausal breast cancer patients treated with anastrozole or tamoxifen: A TransATAC study. Breast Cancer Res. 2012 Apr 4;14(2):R57.
Lundgren K, Brown M, Pineda S, Cuzick J, Salter J, Zabaglo L, Howell A, Dowsett M, Landberg G, - OB. 

ER and HER2 expression are positively correlated in HER2 non-overexpressing breast cancer. Breast Cancer Res. 2012 Mar 14;14(2):R46.
Pinhel I, Hills M, Drury S, Salter J, Sumo G, A'hern R, Bliss JM, Sestak I, Cuzick J, Barrett-Lee P, Harris A, Dowsett M; the NCRI Adjuvant Breast Cancer Trial Management Group. 

CYP2D6 and UGT2B7 Genotype and Risk of Recurrence in Tamoxifen-Treated Breast Cancer Patients. J Natl Cancer Inst. 2012 Mar 21;104(6):452-60.
Rae JM, Drury S, Hayes DF, Stearns V, Thibert JN, Haynes BP, Salter J, Sestak I, Cuzick J, Dowsett M; on behalf of the ATAC trialists. 

Prognostic Value of a Combined Estrogen Receptor, Progesterone Receptor, Ki-67, and Human Epidermal Growth Factor Receptor 2 Immunohistochemical Score and Comparison With the Genomic Health Recurrence Score in Early Breast Cancer. J Clin Oncol 2011 Nov 10;29(32):4273-8.
Cuzick J, Dowsett M, Pineda S, Wale C, Salter J, Quinn E, Zabaglo L, Mallon E, Green AR, Ellis IO, et al.

Prediction of risk of distant recurrence using the 21-gene recurrence score in node-negative and node-positive postmenopausal patients with breast cancer treated with anastrozole or tamoxifen: a TransATAC study. J Clin Oncol., 28(11):1829-34.
Dowsett M, Cuzick J, Wale C, Forbes J, Mallon EA, Salter J, Quinn E, Dunbier A, Baum M, Buzdar A, Howell A, Bugarini R, Baehner FL, Shak S (2010).

Centre for Psychiatry

Funding Body:  National Institute of Health Research - HS&DR Programme (project number 10/1011/

Principal Investigator:  Kamaldeep Bhui,

Overview

Rates of compulsory admission have increased in England in recent decades, and this trend is accelerating.  Studying variation in rates between people and places can help identify modifiable causes. This study quantifies and models variances in the rate of compulsory admission in England at different spatial levels, and assesses the extent to which this was explained by characteristics of people and places.

Cross-sectional multilevel statistical modelling was applied to Mental Health Minimum Dataset (MHMDS) data on 1,287,730 patients in England from 95% of Primary Care Trusts (PCTs), 93% of General Practices and all 69 NHS providers of specialist mental health services.

Funding: NIHR HS&DR Programme (project number 10/1011/70)

Staff

  • Kamaldeep Bhui
  • Scott Weich
  • Orla McBride
  • Liz Twigg
  • Patrick Keown
  • Eva Cyhlarova
  • Helen Parsons
  • Jan Scott

Centre for Cancer Prevention

Funding Body:  CRUK

Principal Investigator:  Professor Peter Sasieni,

OVERVIEW

Researchers from Queen Mary University of London have set up a study to look at whether women who suffer health problems or have riskier lifestyles are less likely to attend cervical cancer screening. The aim of the cervical cancer screening programme is to detect and treat precancerous lesions to avoid the development of cervical cancer. This results in cervical cancer being observed less frequently in women who have attended cervical screening. However it is not clear whether the low risk of being diagnosed with cervical cancer following a normal screening test is due to the screening test alone or whether it also reflects the possibility that those women who attend screening are healthier that those who do not, i.e. they are already at lower risk of cervical cancer than women who do not attend.

TRIAL INFORMATION

To explore whether this phenomenon exists and its magnitude the researchers have setup a record linkage study involving a sample of women who died between 1992 and 2012 and were aged 20-69 in 1992. These women will be compared to women (with a similar date of birth to the women who have died) selected at random from the cervical screening call/recall database. The researchers will not have access to names or full dates of birth/death for the women included in the study. They will know the year and cause of death and the year in which they had a cytology test but no other personal identifiers.

DATA PROCESSING AND PATIENT CONFIDENTIALITY

Queen Mary University of London will collect information about you for this study from NHS Digital, as well as the NHS Cervical Screening Programme. This information will include your month and year of birth and of death, cause of death and month and year of any cervical screening tests. We will use these data to help assess the effectiveness of the cervical screening programme.

As Data Controller, Queen Mary University of London (QMUL) is responsible for the collection, storage and processing of these data for the study. These data include the following potentially identifiable data, categorised under the General Data Protection Regulation (GDPR) as de-identified:

 

  • Mortality data (month and year of death and cause of death);
  • NHAIS cervical screening date (month and year of any screening tests);

The level of data collected from NHS/public health bodies will only be de-identified before it is given to us at QMUL and will not be shared with any third parties. Only authorised staff at the Wolfson Institute of Preventive Medicine are able to access the data and only for specific purposes related to the study. The data is stored in a secure, restricted-access environment. The data will be retained until destruction at the end of the study archiving period, which will be in 2021.

The legal bases for processing this data are exemption from Section 251 of the NHS Act 2006, as well as Article 6(1)(e) ‘performance of a task carried out in the public interest’ and Article 9(2)(j) ‘public interest, scientific or historical research purposes or statistical purposes’ pursuant to the GDPR.

As a University we use personally-identifiable information to conduct research to improve health, care and services. As a publicly-funded organisation, we have to ensure that it is in the public interest when we use potentially-identifiable information. This means that we will use your data in the ways needed to conduct and analyse the research study. To safeguard your rights, we have requested the minimum personally-identifiable information possible. Your rights to access, change or move your information are limited, because we as researchers have only received de-identified data and hence cannot identify any individual from it.

Health and care research should serve the public interest, which means that we have to demonstrate that our research serves the interests of society as a whole. We do this by following the UK Policy Framework for Health and Social Care Research.

If you wish to raise a complaint on how we have handled your personal data, you can contact our Data Protection Officer (data-protection@qmul.ac.uk) who will investigate the matter. If you are not satisfied with our response or believe we are processing your personal data in a way that is not lawful you can complain to the Information Commissioner’s Office (ICO).

QMUL privacy notice can be found at: http://www.arcs.qmul.ac.uk/media/arcs/policyzone/Privacy-Notice-for-Research-Participants.pdf

FURTHER INFORMATION

The researchers hope to publish this research by the end of 2019. For more information on the study or if you would like to know the results once they are published contact Alejandra Castanon at a.castanon@qmul.ac.uk.

Centre for Cancer Prevention

Funding Body:  Cancer Research UK

Principal Investigator:  Professor Jack Cuzick,

Overview

In February 2018, Cancer Research UK funded the AsCaP Project for 5 years to understand the major role aspirin can play in preventing cancer. 

Professor Jack Cuzick is leading an international collaboration of experts including lab researchers, epidemiologists and clinical trial experts from institutes at Queen Mary University of London, Harvard School of Medicine, Newcastle University and University College London to explore why aspirin appears to only have a powerful effect on some cancer types.  There is strong evidence that aspirin reduces the risk of bowel cancer, some evidence it can cut the risk of stomach and oesophageal cancers, and potentially a number of other cancers types. 

The research carried out and supported by AsCaP aims to find out who is likely to benefit most from the drug and who is at greater risk of bleeding side-effects.  The researchers will also investigate what the best dose is, how long to take it for and how aspirin works to reduce cancer risk. 

We also aim to develop future leaders in population research specialised in cancer prevention through PhD and post-doctoral training. 

King's College London

Principal Investigator:  Professor Elinor Sawyer,

Trial Information

1. GLACIER

The GLACIER (A study to investigate the Genetics of LobulAr Carcinoma In situ in EuRope) Study looked at people who had a diagnosis of lobular carcinoma in situ (LCIS) or a type of breast cancer called invasive lobular cancer in order to identify new genes which may have caused this condition to occur, as well as identifying cases of LCIS which may progress to invasive cancer.

Lobular carcinoma in situ (LCIS) is a clinically undetectable form of non-invasive breast cancer, and is typically an incidental finding when a biopsy is performed for another reason. The advent of screening mammography and the increasing breast biopsy rate has meant that a diagnosis of LCIS is becoming more common. Although a diagnosis of LCIS is often an incidental finding, it is significant as it is a risk factor for the development of subsequent invasive breast cancer in either breast, with the majority of these subsequent invasive cancers being invasive lobular carcinomas. Unfortunately the optimum management for LCIS is not known, as we cannot predict those patients who are likely to progress to invasive breast cancer.

The GLACIER study recruited over 2000 women with LCIS or invasive lobular carcinoma over 5 years, and closed to recruitment in 2012. Controls without breast cancer were also recruited to the study.

 

2. ICICLE

The ICICLE (A study to Investigate the genetiCs of In situ Carcinoma of the ductaL subtypE) Study identified patients with a past history or recent diagnosis of ductal carcinoma in situ (DCIS) from participating centres in the UK in collaboration with the National Cancer Research Network with the aims to identify genes which predispose to DCIS, and also to identify those cases which are more likely to subsequently develop invasive cancer.

DCIS is a form of non-invasive breast cancer. Previously it typically presented as a palpable mass. Now with the advent of screening mammography, the majority of cases are diagnosed whilst still clinically occult. Women with a family history of breast cancer are at increased risk of developing breast carcinoma in situ. The aim of this study was to collect a large resource of cases to identify inherited variation that predisposes women to develop DCIS, as current treatment is aimed at preventing disease recurrence but critically it is not possible to predict which women would progress.

The ICICLE Study recruited over 5000 women over 5 years, and closed to recruitment in 2013. Controls without breast cancer also took part in the study.

 

Data Processing & Patient Confidentiality

Follow-up Study

Did you take part in the ICICLE or GLACIER study sponsored by QMUL and led by Rebecca Roylance and Elinor Sawyer?

We are gathering information on those that took part and consented for their data/sample to be used in future studies to see if their cancer has recurred or progressed since the close of these studies.

King’s College London are now looking after the initial studies and the follow-up study, and will be working on the follow-up study alongside Guy’s & St Thomas’ Hospital. If you have any questions please contact Professor Elinor Sawyer (elinor.sawyer@kcl.ac.uk) or Jasmine Timbres (jasmine.timbres@kcl.ac.uk) from the King’s College London Breast Cancer Genetics Team.

Further Information

Sponsorship

The sponsorship for the GLACIER and ICICLE studies changed in 2019 from Queen Mary’s University London to King’s College London, although still under the supervision of Co-Chief Investigator Professor Elinor Sawyer. For more information, contact Professor Elinor Sawyer (elinor.sawyer@kcl.ac.uk) or Jasmine Timbres (jasmine.timbres@kcl.ac.uk).

 

Publications

  • Sawyer, E., Petridis, C., Kohut, K., Gorman, P., Caneppele, M. and Roylance, R. (2012). 121 Risk Factors Associated with Lobular Carcinoma in Situ: Results of the GLACIER Study. European Journal of Cancer, 48, pp.S75-S76. 48. S75-S76. 10.1016/S0959-8049(12)70189-2. https://www.ejcancer.com/article/S0959-8049(12)70189-2/fulltext

 

  • Sawyer, E., Roylance, R., Petridis, C., Brook, M., Nowinski, S., Papouli, E., Fletcher, O., Pinder, S., Hanby, A., Kohut, K., Gorman, P., Caneppele, M., Peto, J., dos Santos Silva, I., Johnson, N., Swann, R., Dwek, M., Perkins, K., Gillett, C. et al. (2014). Genetic Predisposition to In Situ and Invasive Lobular Carcinoma of the Breast. PLoS Genetics, 10(4), p.e1004285. 10.1371/journal.pgen.1004285. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3990493/

 

 

  • Shah, V., Nowinski, S., Levi, D., Shinomiya, I., Kebaier Ep Chaabouni, N., Gillett, C., Grigoriadis, A., Graham, T., Roylance, R., Simpson, M., Pinder, S. and Sawyer, E. (2017). PIK3CA mutations are common in lobular carcinoma in situ, but are not a biomarker of progression. Breast Cancer Research, 19(1).19. 10.1186/s13058-016-0789-y. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5240238/

 

  • Petridis, C., Brook, M., Shah, V., Kohut, K., Gorman, P., Caneppele, M., Levi, D., Papouli, E., Orr, N., Cox, A., Cross, S., dos-Santos-Silva, I., Peto, J., Swerdlow, A., Schoemaker, M., Bolla, M., Wang, Q., Dennis, J., Michailidou, K., Roylance, R., Sawyer, E. et al. (2016). Genetic predisposition to ductal carcinoma in situ of the breast. Breast Cancer Research, 18(1). 10.1186/s13058-016-0675-7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4756509/

 

  • Petridis, C., Arora, I., Shah, V., Megalios, A., Moss, C., Mera, A., Clifford, A., Gillett, C., Pinder, S., Tomlinson, I., Roylance, R., Simpson, M. and Sawyer, E. (2019). Frequency of pathogenic germline variants in BRCA1, BRCA2, PALB2, CHEK2 and TP53 in ductal carcinoma in situ diagnosed in women under the age of 50 years. Breast Cancer Research, 21(1). 21. 10.1186/s13058-019-1143-y. https://www.ncbi.nlm.nih.gov/pubmed/31060593

Centre for Prevention, Detection & Diagnosis, Wolfson Institute of Population Health, Queen Mary

Principal Investigator:  Professor Ranjit Manchanda ,

 

Overview

The COVID-19 pandemic has created unprecedented changes in gynaecological cancer treatment delivery in the UK, with many aspects of the patient pathway affected and treatments prioritised and modified. The UK Covid and Gynaecological Cancer Study (UKCOGS) is a multi-phased project recording and assessing changes and outcomes in patient care across the patient pathway, within the multi-disciplinary team context.

Aims

  • To evaluate the MDT decision making for gynaecological cancer, patients outcomes across the UK in response to the COVID-19 pandemic.
  • To document the structural and logistic changes implemented across Gynae-oncology cancer centres in response to the COVID-19 pandemic.

The first phase of this project is a national audit of the impact of the COVID-19 pandemic on treatment recommendations for patients made through multi-disciplinary team (MDT) clinic meetings.

The project is endorsed by the British Gynaecological Cancer Society (BGCS), Royal College of Obstetricians and Gynaecologists (RCOG), the NCRI Gynaecological Cancer Clinical Studies Group, the British Association of Gynaecological Pathologists (BAGP), The Eve Appeal, Target Ovarian Cancer, Ovarian Cancer Action, Ovacome, Jo’s Cervical Cancer trust and GO Girls

UKCOGS Co-Leads:

Ranjit Manchanda, Sadaf Ghaem-MaghamiSean Kehoe

 

 Logos of the organisations funding the UKCOGS study

Trial Information

Information for patients:

COVID-19 caused huge disruption to patients across the country. This affected patients who were having tests for cancer, and those with confirmed cancer. Many patients had their tests and treatments delayed or cancelled. This included important treatments such as surgery and chemotherapy. This sometimes happened to reduce the risk of infection, or because of a lack of staff or operating theatres.

All patients having tests or treatments for cancer are discussed by a team of specialist doctors and nurses. This is called a multi-disciplinary team (MDT). All discussions are recorded. MDTs also record whether there were any delays or cancellations due to COVID. We are combining this information from hospitals across the country. This helps us to build a national picture of what happened during the pandemic. 

We want to understand what level of disruption happened to cancer patients due to COVID. We also want to find out whether this disruption affected the health or survival of those patients. We want to know whether patients with cancer during COVID were more likely to have their cancer return, to have long-term health problems, or to not live as long.

We believe this is very important, and we will use the results to better prepare the NHS for the future.

Our team

We are a team of cancer doctors and researchers from around the UK. We specialise in cancers of the ovary, womb, cervix, and vagina. We are experienced at running projects like this.

The main investigator of this project is Professor Ranjit Manchanda, of Queen Mary University of London. The other leads are Professor Sadaf Ghaem-Maghami and Professor Sean Kehoe. Around 50 hospitals are taking part.

Our supporters

This audit is endorsed by professional societies: the British Gynaecological Cancer Society (BGCS), Royal College of Obstetricians and Gynaecologists (RCOG), the NCRI Gynaecological Cancer Clinical Studies Group, and the British Association of Gynaecological Pathologists (BAGP).

 We also have support of charities including The Eve Appeal, Target Ovarian Cancer, Ovarian Cancer Action, Ovacome, Jo’s Cervical Cancer trust and GO Girls

Taking part

You do not have to do anything to take part in this. Information about your care may be used in this audit if:

  • You had tests for suspected cancer, or a diagnosis of cancer
  • Your care was discussed by an MDT at one of the hospitals involved in the audit
  • This discussion occurred between March 2020 and March 2021

 The 'News' section has a list of all the hospitals involved in this audit. 

The information that we will be recording

Since March 2020, we have gathered information from 50 hospitals. This includes how many delays or changes there were to cancer tests and treatments. This does not contain any information that identifies any patients.

We want to find out the long-term impact of these changes. To do this, we need to access the NHS records of these cancer patients. This allows us to check whether a patient attends hospital in future, if their cancer returns, and how long they survive for. We are applying to the NHS Health Research Authority for approval for this.

If this approval is given, this data would be held on a secure database at Queen Mary University of London. Only a few approved staff will be allowed to see any patient records. Most of the team will only be able to see anonymous data, and could not identify any patients. The results of this audit will not include any information about individual patients.

All data about patients will be highly confidential. This will not be released to anyone outside the audit. There are strict processes to ensure this information is safe and secure.

Contacting the team

You can contact us if you have any questions about this, including how your data will be used. You can also contact us if you wish to opt-out of your data being used in this audit. You do not have to give a reason.

Our contact details are:

Email: bcc-ukcogs@qmul.ac.uk

Telephone: 020 7882 3550

Post:
UKCOGS Team,
Wolfson Institute of Population Health,
Charterhouse Square,
London EC1M 6BQ

Choosing to opt out of this audit means that the information that the NHS holds about you will not be available to researchers. This means the team will not monitor the long-term effects of changes to your treatment. This will NOT affect your medical care in any way. Your doctors will not be aware of whether you take part in this or not.

News

Our Participating Sites

Airedale NHS Foundation Trust

Aberdeen Royal Infirmary

Barnsley Hospital NHS Foundation Trust

Barts Health NHS Trust

Basingstoke and North Hampshire Hospital

Belfast City Hospital

Queen's Hospital Burton

Cambridge University Hospitals NHS Foundation Trust

Guy's and St Thomas' NHS Foundation Trust

Royal Derby Hospital

East Kent Hospitals University Foundation NHS Trust

Royal Bolton Hospital

Imperial College London

Ipswich Hospital

Leeds Teaching Hospitals NHS Trust

Ninewells Hospital Dundee

North Wales Surgical Cancer Centre

Northampton General Hospital

Northern Gynaecological Oncology Centre Gateshead

Nottingham University Hospitals NHS Trust

Oxford University Hospitals NHS Foundation Trust

Pan Birmingham Gynaecological Cancer Centre

Poole Hospital NHS Trust

Royal Cornwall Hospitals NHS Trust

The Royal Marsden NHS Foundation Trust

Royal Preston Hospital

Royal Surrey NHS Foundation Trust

Royal United Hospitals Bath

St Mary's Hospital Manchester University

Sheffield Teaching Hospitals NHS Foundation Trust

Somerset NHS Foundation Trust

South East Scotland Cancer Network

Southend University Hospital

Stepping Hill Hospital

Swansea Gynaecological Oncology Centre

The Royal Wolverhampton Hospital

University College London Hospitals NHS Foundation Trust

University Hospital Lewisham

County Durham & Darlington NHS Foundation Trust

University Hospital of Wales Cardiff

University Hospitals Bristol NHS Foundation Trust

University Hospitals Coventry and Warwickshire NHS Trust

Royal Hampshire County Hospital Winchester

Wirral University Teaching Hospital NHS Foundation Trust

Worcestershire Acute Hospitals NHS Trust

Further Information

UKCOGS Steering Committee:

Dr Andy Nordin (Chair, Steering Committee, Consultant Gynaecological Oncologist, East Kent, Margate)

Dr Simon Leeson (Consultant Gynaecological Oncologist, North Wales Gynaecological Cancer Surgical Centre)

Dr Stephen Dobbs (Consultant Gynaecological Oncologist, Belfast Health and Social Care Trust)

Mr Kevin Burton (Consultant Gynaecological Oncologist, Glasgow Royal Infirmary)

Professor Sudha Sundar (BGCS President, Consultant Gynaecological Oncologist, Birmingham University)

Dr Shibani Nicum (Chair NCRI Gynae CSG, Consultant Medical Oncologist, University of Oxford)

Professor Glenn McCluggage (Consultant Histopathologist, BAGP, Queens University of Belfast)

Ms Helen Manderville (Clinical Nurse Specialist)

Dr Alex Taylor (Consultant Clinical Oncologist, Royal Marsden Hospital)

Professor Evis Sala (Consultant Radiologist, Addenbrookes Hospital, University of Cambridge)

Dr Adam Brentnall (Statistician, WIPM, Queen Mary University of London)

Professor Rhian Gabe (Director, Barts Clinical Trials Unit, WIPM, Queen Mary University of London)

Dr Rosa Legood (Health Economist, London School of Hygiene & Tropical Medicine)

Patient representative (TBC)

Professor Ranjit Manchanda (Wolfson Institue of Preventive Medicine, Queen Mary University of London)

Professor Sadaf Ghaem-Maghami (Imperial College)

Professor Sean Kehoe (Birmingham University)

Logos of the universities collaborating on the UKCOGS study

Staff

UKCOGS Co-Leads:

Professor Ranjit Manchanda (Wolfson Institue of Preventive Medicine, Queen Mary University of London)

Professor Sadaf Ghaem-Maghami (Imperial College)

Professor Sean Kehoe (Birmingham University)

Director Trials Unit:

Professor Rhian Gabe (Wolfson Institue of Preventive Medicine, Queen Mary University of London)

Statistician:

Dr Adam Brentnall (Wolfson Institue of Preventive Medicine, Queen Mary University of London)

 

Centre for Psychiatry

Principal Investigator:  Peter White, Professor T Chalder, Kings College London, Professor M Sharpe, University of Oxford ,

Status: ending

PACE was a randomised controlled trial that involved 641 UK patients suffering from Chronic Fatigue Syndrome (sometimes referred to as Myalgic Encephalomyelitis) and was co-led by investigators based at Queen Mary University of London, King’s College London and the University of Edinburgh.

The study compared the effectiveness of four of the main treatments and found that, when added to specialist medical care, cognitive behaviour therapy and graded exercise therapy were more effective than both adaptive pacing therapy and specialist medical care alone.

Overview

What is the PACE trial?

This large-scale trial is the first in the world to test and compare the effectiveness of four of the main treatments currently available for people suffering from chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis (ME). These are adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and standardised specialist medical care (see below). All of the treatments offer ways for patients to deal with and improve the symptoms of CFS/ME and its effects on disability. The participants in the trial are randomly allocated to one of the treatments and then given a 12-month programme involving appointments with specialised doctors and, for three of the four treatment groups, therapists. Participants' progress is closely monitored by specially-trained research nurses or assistants. The five-year trial will involve 600 participants, aged 18 and over, in Scotland and England. All have to be referred from the specialist hospital CFS/ME clinics involved in the trial and these are based in Edinburgh, Oxford and three London hospitals.

What is CFS/ME?

CFS/ME is a common disorder. Estimates vary, but it is believed that between one in 40 and one in 250 of the population will suffer from the illness at any one time. CFS/ME causes disability as a result of persistent, abnormal tiredness which is made worse by activity. Other symptoms can include disturbed or unrefreshing sleep, or sleeping for longer, problems concentrating or remembering, pain in the muscles and/or joints, headaches, sore throats and tenderness in the neck. The diagnosis of CFS/ME sometimes can be difficult because it requires that a large number of other possible causes of the symptoms, such as thyroid gland disease and severe depression, are excluded.

What are the treatments being tested?

The four treatments are standardised specialist medical care (SSMC) alone, SSMC plus adaptive pacing therapy, SSMC plus cognitive behaviour therapy and SSMC plus graded exercise therapy. The therapies are delivered, as appropriate, by occupational therapists, physiotherapists, clinical psychologists or by other healthcare staff with specialist training.

  • Standardised specialist medical care. This is the most common treatment for CFS/ME. Specialist doctors can give an explanation of why participants are ill and general advice about managing the illness. They may also prescribe medicines to help with troublesome symptoms such as insomnia and pain, or advise GPs on what medicine is appropriate. If a participant is randomised to this treatment alone, they are encouraged to use specific self-help management that make most sense to them.
  • Adaptive pacing therapy. This therapy is about carefully matching activity levels to the amount of energy available. Therapists work with participants in this treatment group to help monitor activity and symptoms, aiming to improve quality of life and create the best conditions for a natural recovery.
  • Cognitive behaviour therapy. This therapy is about examining how thoughts, behaviour and CFS/ME symptoms interact with each other. Between therapy sessions, participants in this treatment group are encouraged to try out new ways of coping with their illness.
  • Graded exercise therapy. This is about gradually increasing physical activity to improve fitness and get the body used to activity again. A therapist helps participants in this treatment group to work out a basic activity routine and slowly build up the amount of exercise as fitness increases.

Trial Information

Trial Meeting Minutes

PACE Data Sharing Policy [PDF 179KB]

July 2015 update: Analysis of mediators paper published
http://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(14)00069-8/abstract

Other papers recently published include:

The statistical plan for the trial:
http://www.biomedcentral.com/content/pdf/1745-6215-14-386.pdf
Recovery as an outcome:
http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=8988741&fileId=S0033291713000020
Pain as an outcome:
http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=9215309&fileId=S0033291713002201
How we did the trial:
http://pb.rcpsych.org/content/39/1/24.short

Here is a paper that describes an independent Cochrane review of exercise therapy in CFS, which included the PACE trial:
http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD003200.pub3/epdf/standard

21 September 2012 update: Health economics paper, including cost-effectiveness comparisons, has now been published in PLOS ONE, and is available for free download at this link.

11 March 2011 update: Full PACE paper and web appendix now available to download free of charge here

18 February 2011 update: Participants' newsletter issue 4 now available (see below)

17 February 2011 update: PACE treatment manuals available

Treatment manuals (all PDFs): The treatment manuals are available free of charge for down-loading, so long as no changes are made to the manuals. Any use of these manuals should acknowledge the PACE trial (www.pacetrial.org). These manuals were used in the PACE trial by healthcare professionals and participants to support PACE trial treatments, which are described in the manuals. The results regarding efficacy and safety of these treatments are not yet published, but will be reported in the main paper of the PACE trial.

These treatments should only be delivered by appropriately qualified healthcare professionals, who have received appropriate training and continued supervision in their use. The treatments described were not designed to be stand-alone self-help approaches. No responsibility is accepted by the authors for the application of treatments described in these manuals outside of the PACE trial. The PACE trial team are unable to respond to queries or comments regarding the use of these manuals or the treatments described.

1. APT Therapist Manual.pdf [PDF 681KB]

2. APT Particpant Manual.pdf [PDF 286KB]

3. CBT Therapist Manual.pdf [PDF 452KB]

Appendix to (3) [DOC 82KB]

4. CBT Participant Manual.pdf [PDF 385KB] NB copyright © Constable and Robinson

Appendix to (4) [DOC 185KB]

5. Get Therapist Manual.pdf [PDF 446KB]

6. GET Participant Manual.pdf [PDF 421KB]

7. SSMC Doctor Manual.pdf [PDF 211KB]

March 2010 update: Data collection for the one year follow up has now been completed. The trial data is currently being analysed in preparation for publication of the findings. Further information regarding publication will be posted here when available.

For information on the trial given to potential participants, please download Trial Information.pdf [PDF 41KB]

Patient Clinic Leaflet.pdf [PDF 29KB] (PDF, 30 KB)

Participants' newsletters (all PDFs):

On-line trial protocol published on BioMed Central

Lead co-principal investigator Professor PD White
Co-principal investigators: Professor T Chalder, Kings College London, Professor M Sharpe, University of Oxford

News

20 May 2020: The Health Research Authority have commended the conduct of the PACE trial, following an investigation into the trial. The Chairman of the HRA, Professor Sir Jonathan Montgomery, wrote: “Our review suggests that the PACE trial exceeded expectations in its transparency when judged against contemporary expectations. … We commend the investigators of PACE for recognising the importance of transparency by acting on good practice recommendations for publication on protocols and the statistical analysis plan even though they are not regulatory requirements.”  Regarding potential conflicts of interest, Professor Montgomery wrote: “ We have concluded that there is no basis for individual criticism here, but that we should work with stakeholders to consider whether expectations for disclosures should be redefined for the future to meet current participant expectations.” In summary, Professor Montgomery wrote: “We have therefore concluded that there are no regulatory concerns about the conduct of the investigators in relation to these issues.”  https://www.parliament.uk/documents/commons-committees/science-technology/Correspondence/190129-Sir-Jonathan-Montgomery-Health-Research-Authority-to-Chair-re-PACE-trial.pdf

Comment from the BMJ can be found here: https://search.proquest.com/openview/50b7d9b4a5b9693a1d6342d89aea95a3/1?pq-origsite=gscholar&cbl=2043523 

9 September 2016 Statement: Release of individual patient data from the PACE trial

8 September 2016: PACE trial team analyse main outcome measures according to the original protocol

PACE_bimodal_CFQ_analysis_final_8_Sept_2016.pdf [PDF 224KB]

PACE_published_protocol_based_analysis_final_8th_Sept_2016(1).pdf [PDF 229KB]

16 August 2016 Statement: Release of individual patient data from the PACE trial

18 December 2015 Statement: Release of individual patient data from the PACE trial

Government support for the PACE trial [PDF 55KB]

21 September 2012 update: Health economics paper, including cost-effectiveness comparisons, has now been published in PLOS ONE, and is available for free download at this link.

11 March 2011 update:

Full PACE paper and web appendix now available to download free of charge, after registering with The Lancet

18 February 2011 update:

Results now available at The Lancet Participants' newsletter issue 4 now available under the Trial information tab

17 February 2011 update: PACE treatment manuals available

The treatment manuals are available, free of charge, under the Trial Information tab for downloading, so long as no changes are made to the manuals. Any use of these manuals should acknowledge the PACE trial (www.pacetrial.org). These manuals were used in the PACE trial by healthcare professionals and participants to support PACE trial treatments, which are described in the manuals. The results regarding efficacy and safety of these treatments are not yet published, but will be reported in the main paper of the PACE trial.

These treatments should only be delivered by appropriately qualified healthcare professionals, who have received appropriate training and continued supervision in their use. The treatments described were not designed to be stand-alone self-help approaches. No responsibility is accepted by the authors for the application of treatments described in these manuals outside of the PACE trial. The PACE trial team are unable to respond to queries or comments regarding the use of these manuals or the treatments described.

March 2010 update: Data collection for the one year follow up has now been completed. The trial data is currently being analysed in preparation for publication of the findings. Further information regarding publication will be posted here when available.

Further Information

FAQ

Previous Frequently Asked Questions (FAQs)

faq1.pdf [PDF 20KB]
faq2.pdf [PDF 94KB]
faq3.pdf [PDF 178KB]

Current FAQs

Patients, diagnoses and trial entry

What is Chronic Fatigue Syndrome?
Chronic Fatigue Syndrome (CFS) is an illness in which a person is disabled by severe fatigue and other symptoms, which have lasted at least six months, and there is no other disease found that could explain the symptoms.

How is CFS defined?
Several published definitions or criteria can be applied to decide if a person has CFS. We used the Oxford definition (see below) to define CFS in the PACE trial.

We also assessed participants to see if they met the International (Centers for Disease Control) definition, to see whether the effects of treatments were different in those who met this alternative definition. 67 per cent of PACE trial patients met this definition.

What is ME?
ME or myalgic encephalomyelitis/encephalopathy refers to an illness in which severe fatigue is a symptom, which is characteristically exacerbated by minimal activity, along with other symptoms that fluctuate over time.

We assessed whether patients in the PACE trial met the London criteria for ME. We did this to see whether the effects of treatment differed in those who met criteria for ME. 51 per cent of PACE trial patients met the London criteria for ME.

What is the difference between CFS and ME?
The relationship between the two conditions is controversial. However, it is generally agreed that ME is a similar or related condition to CFS; some regard it as the same condition; others believe it to be a distinct illness.

What are the “Oxford” criteria for CFS?These require that a person has had at least six months of severe fatigue, that fatigue is their main symptom, and that the fatigue is disabling and accompanied by other symptoms. It is also required that the person has no other medical condition that could explain the symptoms. All patients in the PACE trial met these criteria.

Why did you choose the Oxford criteria for defining CFS?
There is no “gold standard” definition of chronic fatigue syndrome, and around 20 definitions have been published. We chose the Oxford criteria because: (a) we wanted to find out which treatments were best in those who had fatigue as their principal symptom. Some patients, clinically diagnosed as having CFS, may have another symptom, such as pain, as their primary symptom. (b) The Oxford definition of CFS is the most straightforward to use in clinical practice and has been used in many previous research studies. We also assessed participants to see if they met the International (Centers for Disease Control) criteria for CFS.

Did you include people who did not have CFS?
The study used stringent procedures to ensure that those people with another diagnosis that would explain their fatigue were excluded. These included a full history and physical examination by a specialist doctor, ten blood tests and a urine test. All potential participants also underwent a standardised psychiatric interview. Together these procedures ensured that patients entering the trial were suffering from CFS.

Did you include people with ME?
Half (51 per cent) of trial participants met criteria for ME, as defined by the London criteria, which were based on the original description by the late Dr Melvin Ramsay, physician at the Royal Free Hospital. The trial results for people who met criteria for ME were the same as for those who did not.

The trial and treatments

What treatments did you test?
Participants were randomly allocated to one of four treatment groups. All participants received specialist medical care (SMC). One group received this alone. The other three groups also received either adaptive pacing therapy (APT), cognitive behaviour therapy (CBT) or graded exercise therapy (GET). All treatments were delivered on an individual basis.

Specialist Medical Care (SMC) consisted of seeing a doctor in a clinic that specialised in the management of CFS. This included providing general advice about managing the illness and prescribing medicines for symptoms such as sleep problems and pain, as well as encouraging self-help when SMC was provided by itself without an additional therapy.

Adaptive Pacing Therapy (APT), delivered by occupational therapists, assumed that the illness could not be changed by changing behaviour, and aimed to help the patient to use their energy wisely and to allow natural recovery, by both stabilising and balancing activities with rest, while staying within the limits imposed by the illness. All participants also received Specialist Medical Care (SMC).

Cognitive behaviour therapy (CBT) was provided by a clinical psychologist or nurse therapist. After stabilising the level of activity, CBT aimed to help the patient to do more and feel better by testing out the best ways to cope with the illness. This included a gradual return to activities and challenging what both patients and therapists had identified as potentially unhelpful ways of coping and thinking about the illness. All participants also received SMC.

Graded exercise therapy (GET) was delivered by physiotherapists and consisted of an individually tailored exercise programme. This began with stabilisation of levels of activity and then incremental increases in physical activity, agreed between participant and physiotherapist. The planned increments took into account symptoms, fitness, and current activity levels. The treatment aimed to help patients do more and feel better by gradually increasing the time they were physically active and then increasing the intensity of activity. All participants also received SMC.

Why did you select these treatments for study?

CBT and GET had been shown in previous small trials to be moderately effective treatments for patients with CFS. However, some patient organisations had expressed concern about their safety and efficacy, and had reported that patients preferred pacing or specialist medical care. We therefore wanted to find out which treatments were both safe and effective.

Is it a problem that participants were not blinded to the treatments being received?
Both the therapists and patients knew what treatments they were being given. This is unavoidable for trials of rehabilitative treatments in which the patient is an active participant.

The statistician doing the main analysis did not know which treatment group participants were in (treatment groups were labelled A, B, C or D), to avoid any potential bias in the conduct of the analysis.

Was the treatment effect due to the participants choosing a particular treatment?
The allocation of treatment to participants was random and patients could not select which treatment they received.

Was the treatment effect due to some participants getting more attention than others?
This is very unlikely as the three additional therapies were closely matched for amount of patient contact.

Was the treatment effect due to participants expecting to get better with CBT or GET?This is also very unlikely as we measured participants’ expectations of their allocated treatment, after they knew which one they were getting and before they started it. This indicated that patients expected CBT to be least likely to be helpful. Despite this, CBT emerged as one of the two treatments that helped the most. In contrast, patients about to receive adaptive pacing therapy had the highest expectations of benefit, but this was the least effective. This all suggests that the participant’s expectations of treatment did not determine the trial outcomes.

During the trial, a newsletter was distributed that contained quotes from participants. Could this have caused bias in the study?
It is considered good practice to publish newsletters for participants in trials, so that they are kept fully informed both about the trial’s progress and about news of developments in their illness.

The investigators published four such newsletters during the trial, which can all be found here, and all newsletters were approved by the independent research ethics committee before publication.

For example, in this Newsletter [PDF 395KB], there are six comments from patients about their treatments, but no specific treatment or therapy is named, and investigators were careful to print feedback from participants from all four treatment arms. We included these comments to try to encourage patients to consider entering the trial, in order to improve recruitment. However, by the time it was published, following ethical approval, all participants had been recruited. It would have been very unlikely that the newsletter could have biased participants as any influence on their ratings would affect all treatment arms equally.

The same newsletter also mentioned the publication of the UK National Institute for Health and Care Excellence guideline for the management of CFS (this institute is independent of the UK government). The guidelines were described in summary form, and the only reference made to individual therapies was in the following sentence: “The guidelines emphasise the importance of joint decision making and informed choice and recommended therapies include Cognitive Behavioural Therapy, Graded Exercise Therapy and Activity Management.” These three therapies were the ones being tested in the trial. It is therefore unlikely that it would lead to bias in the direction of one or other of these therapies

The findings <

What did the PACE trial show?
Both cognitive behaviour therapy (CBT) and graded exercise therapy (GET), when combined with specialist medical care (SMC), were more effective in reducing fatigue and improving physical functioning than either adaptive pacing therapy (APT) when combined with SMC, or SMC alone. Approximately 12 out of 20 patients made a clinically useful reduction in fatigue and improvement in functioning with either CBT or GET compared to about 8 out of 20 with APT and 9 out of 20 with SMC.

Twelve months after starting in the trial, 3 out of 10 participants were within normal population ranges for both fatigue and function, following CBT and GET, which were approximately twice as many participants than after APT and SMC. This means patients were more able to do things we all take for granted such as carrying shopping, or walking up a flight of stairs. This level of improvement is what we would expect in the treatment of other chronic disabling conditions. Being within the normal population range for these two outcomes does not necessarily mean the patient had recovered from CFS.

Have any other studies found similar results to the PACE trial?The main results of the study have been verified by a reanalysis of the trial data by a Cochrane Review group. Furthermore a number of published systematic reviews and meta-analyses have supported the findings. These include Whiting et al, 2001, Edmonds et al, 2004, Chambers et al, 2006, Malouff et al, 2008, Price et al, 2008, Castell et al, 2011, Larun et al, 2015, Marques et al, 2015 and Smith et al, 2015.

How effective were CBT and GET?
We concluded that both CBT and GET were more effective than APT and SMC and that the size of the effect was moderate. We drew these conclusions based on the size of their effect compared with APT and SMC and the proportions of participants who made a clinically useful reduction in fatigue and improvement in functioning.

Why did CBT and GET have similar effects? Is it just the effect of seeing a therapist?
Both CBT and GET were better than APT, so this suggests it was not simply due to the benefit of seeing a therapist. The better outcome may have been due to the active rehabilitative approach common to both CBT and GET, which encourages people gradually to do more. However, we have now analysed in more detail what makes these treatments work, and have reported these findings (also explained in a previous FAQ document [PDF 178KB]).

Were the treatments safe?
We measured the safety of all the treatments in five separate ways, and found no significant differences in any of these measures among the different arms of the trial. We concluded that all these treatments are safe so long as they are delivered by similar healthcare professionals, who are trained and supervised to deliver these treatments in a similar way to the PACE trial.

Are the results applicable to those worst affected?
We do not know, as we did not study housebound participants. Results cannot therefore be extrapolated to those who are severely affected.

Does adaptive pacing therapy (APT) not work?
A minority of people who received APT did improve, but no more than the proportion who received SMC by itself. The majority of patients who received APT reported that they were satisfied with their therapy, but more than any other treatment APT was more likely to lead to worse physical functioning.


How is it possible that APT had the most satisfied group of patients but was the least effective therapy?
Satisfaction with a treatment is based on lots of things, such as how helpful the person found their therapist, and does not necessarily relate to its effectiveness. Patients can be satisfied that their therapist did their best, without the therapy itself improving symptoms and disability.

Did poor delivery of APT account for the findings?
We know the therapists delivered APT to a high standard and that APT was delivered as planned because of:

1. The high rates of patient satisfaction,
2. Recorded therapy sessions were consistent with the therapy manual when independently assessed,
3. The quality of the therapeutic relationships between patients and therapists, which were independently assessed, were as good with APT as with other therapies.

This suggests that it was the content of the therapy that was less effective, not the therapists or how it was delivered. It seems as though the adaptive nature of APT is not as effective as the rehabilitative approach common to both CBT and GET.

Would there be additional non-specific effects of seeing a therapist that could have influenced the results?
The non-specific effects of a therapist can be important. However, they would only account for the different outcomes between treatments if there was a difference in how the therapies were delivered between the treatment groups.  It is unlikely that this was the case in the PACE trial. We ensured that all therapists were well trained and supervised, and that the total number of treatment sessions and time offered was the same across all therapies. Patients reported that they were similarly satisfied after all three therapies (APT, CBT and GET). Independent scrutineers of audio recordings of therapies reported that the therapies had been delivered as intended. In summary, it seems improbable that the differences between the therapy groups could be due to non-specific effects.

If the treatments received after the end of the trial and before the 2.5 year follow up were no longer allocated randomly, would this make the results harder to interpret?
Yes it did. After the end of the main study (one year post-treatment) participants were able to choose further treatments if they wished, thus breaking the original randomisation. In clinical trials, it is considered unethical to deny additional treatments to patients following the main phase of a trial if they are requested or needed.

In the findings of the 2.5 year follow up study it was noted that the originally randomly allocated treatment had often been supplemented by an additional treatment, and that this would limit what we could learn by comparing patients in their originally randomised treatment groups.

However, the main findings of the long-term follow were clear – that there was no deterioration from the one year improvements in patients originally allocated to CBT and GET. 

Measuring the outcomes of the trial

Why did you choose a fatigue questionnaire and a scale measuring physical function as the primary outcome measures?
After discussion with patients and a national patient charity, we decided that these measures best captured improvement in the patients’ main symptoms and ability to do things, whilst not being too long or complicated to score.

What is the Chalder fatigue questionnaire?
This 11 item scale measures different aspects of fatigue, and was scored by the trial participants to provide an overall measure of fatigue and associated symptoms; the higher the score the more severe the fatigue.

What is the SF-36 physical function scale?
This 10 item sub scale (from a scale with 36 items) measures different aspects of physical ability. It was used to provide a measure of overall physical function; the higher the score the better the physical function.

Why did you use subjective outcomes?
Following consultation with a patient charity, we chose (subjective) self-ratings as the primary outcomes, since we considered that the patients themselves were the best people to determine their own state of health.

We have also reported the results of a number of potentially more objective outcomes (although all are also dependent on subjective factors of motivation and confidence), including a walking test, a stepping test, employment status and financial benefits, in papers published in the Lancet, PLoS One and Lancet Psychiatry.

The distance participants could walk in six minutes was significantly improved following GET, compared to other treatments.

There were no significant differences in fitness, employment or welfare benefits between any of the treatments. In fact, the numbers of patients receiving welfare benefits went up in all treatment groups, perhaps because they were given a definite diagnosis, and received advice regarding eligibility for welfare benefits during the trial. Treatment manuals can be found here which include the advice regarding welfare benefits and work.

We interpreted these data in the light of their context and validity. For instance, we did not use employment status as a measure of recovery or improvement, because patients may not have been in employment before falling ill, or they may have lost their job because of being ill. Getting better and getting a job are not the same things, and being in employment depends on the prevailing state of the local economy as much as being fit for work.

Note: The above question has been answered elsewhere in 2008, 2011, 2013 (here and here) and 2015.

Could changes in the scoring of the two primary outcomes from the original trial protocol have caused bias?
The two primary outcomes for the trial in the original trial protocol were the SF-36 physical function sub-scale and the Chalder fatigue questionnaire. These were not changed.

However, as a trial like PACE takes many years to complete, discussion about how best to analyse the findings continued after it began, but before any data was analysed.  These discussions led to changes in how we analysed the two primary outcomes (fatigue and physical function). The two independent oversight committees approved the changes. The detailed analysis plan, including these changes, was published, and these changes and the reasons for them were also described in the main paper.

The changes were

A.    Simplifying the main analysis. Originally the analysis was going to use a more complex measure, which combined two ways to measure improvement (the number of patients who either exceeded a threshold score or who improved by more than 50 per cent). After careful consideration, it was decided that this composite measure would be very hard to interpret clinically, and would not allow the direct comparison of effectiveness between treatments. We therefore chose to compare mean (average) scores of each outcome measure. This is a better way to see which treatment works best on which outcome, and made the main findings easier to understand and interpret.

B.    To use the Likert scoring method rather than the binary methods originally proposed for the fatigue questionnaire. This change was to achieve greater variability in the score and greater sensitivity to change. This is because the Likert method allows the questionnaire answers to have a score of 0, 1, 2 or 3 to indicate how much of a problem each fatigue factor is for the participant;  11 questions therefore gives a  score that can range from 0 to 33. The binary method of scoring only considers a yes or no; 11 questions can therefore only produce a range of 0 to 11. Both Likert and binary methods of scoring have been described before and both are regularly used by other researchers.

There were no changes to the scoring method of the physical function scale

These changes have been explained in several publications (here and here), including explicit descriptions and justification within the main paper itself, the statistical analysis plan, and the trial website section of frequently asked questions, published in 2011 [PDF 94KB].

 

Were some of the patients well when they entered the trial?
All patients entering the trial met the Oxford criteria for CFS and also had scores above thresholds of severity for fatigue and physical function. Some 13 per cent had scores within the normal population range (defined as within one standard deviation of the population means) for either one or other of fatigue and physical function. This is not the same as being well or as being ‘recovered’ (see below).

After an editorial suggested that having scores within the normal population range was consistent with recovery, the authors published a correction to clarify that this was not the case.

Did the trial look at recovery?
The main trial report did not address recovery. Recovery is a complex concept that is hard to define.

We did, however, look at recovery in an exploratory secondary analysis of different criteria and explored different ways of defining it.

Why did you change the criteria for determining recovery from the original protocol in the secondary analysis?
Over the long period from writing the original protocol to planning the analysis, we reconsidered our original definition of recovery. As a result, we tried to improve how we measured the concept of recovery and the different ways it can be defined.

For instance, we included those who felt “much” (and “very much”) better in their overall health as one of the five criteria that all had to be fulfilled to define recovery.

We also changed the thresholds for judging recovery on the two primary outcomes (fatigue and physical function) from the mean (average) for the population to the population mean plus a standard deviation from the mean, to better reflect the levels of fatigue and physical function found in the general population. This was informed by a recently published population study.

These changes were all made before the analysis occurred (i.e. they were pre-specified) and were fully described and explained in the paper itself. Furthermore, in the relevant paper we discussed the difficulties in measuring recovery, and showed how other ways of defining recovery could produce different results. The bottom line was that, however we defined recovery, significantly more patients had recovered after receiving CBT and GET than after other treatments.

Why did you not use more objective measures of recovery, such as employment or the distance walked in six minutes, in the secondary analysis?
We addressed this point in 2013 in correspondence that followed the paper. In summary, we did not think that being employed was the same as being recovered, since it was likely that some participants were not working before they became ill, or that they may have lost their job because of being ill. Many factors affect whether a person gains new employment.

We also explained that we did not use the distance walked in six minutes, as we were unable to use this measure in a way comparable to other studies, due to lack of space in some of our clinics and our concern not to exacerbate ill health in patients undertaking this test. Furthermore, some 18 per cent of participants did not undertake this test at follow up.

Implications

Do the results suggest that CFS is ‘all in the mind’?
The study did not find that CFS is ‘all in the mind’ – in fact, it did not look at causes of the disease at all.

Some people may think that if treatments like CBT help CFS patients, it is saying something about the nature of the illness, but this is not true. In the main results paper it was stated:  "The effectiveness of behavioural treatments does not imply that the condition is psychological in nature."

The study tells us nothing about the cause of the illness, simply how effective different treatments are for helping people who have it.

The team that designed and ran the trial include many doctors and healthcare professionals who have worked and continue to work in chronic fatigue syndrome clinics, sometimes for many years.

They are aware of the serious and debilitating nature of chronic fatigue syndrome, and have witnessed in their clinics how the illness can ruin people’s lives and affect their families. There is no doubt in their minds that the illness can last for years and is a real and chronic condition, and they do not think CFS is ‘all in the mind’ or imaginary.

Some of those involved in the PACE trial also undertake research into the biological nature of the illness; research that has indicated that there are some biological abnormalities that have been found repeatedly in CFS.

How have you found a treatment to be useful when we do not know the cause of CFS?
There are very many examples in medicine where a treatment is developed for an illness before the cause of the illness is known. For example: quinine treating malaria, or digitalis (digoxin from the foxglove) helping heart failure. Treatments sometimes help in reversing the factors that keep someone unwell rather than addressing original causes. Digitalis is an example of that. CFS and ME are extremely debilitating and therefore there is a real need for treatment now. We are open minded about what research into the condition’s causes will reveal; in the meantime the PACE trial shows that CBT and GET can make a difference to patients’ lives today.

Why did not all participants improve?
Since approximately 6 out of 10 patients improved after either cognitive behavioural or graded exercise therapies, the results of this study are encouraging. But, as with treatments in most areas of medicine, there will be patients who do not respond to treatment. This underscores the need for continued research into this area.

Does the PACE trial say that CBT and GET are the only treatments for CFS?
The trial found CBT and GET to be moderately helpful and also that they do not benefit everyone. All patients also received specialist medical care, which might involve being prescribed medicines to help symptoms such as insomnia or pain.

It has always been recognised that more research is needed to find other treatments that help. This was recently stated in the results of the 2.5 year follow up when it was noted that in all of the treatment groups some patients remained unwell at long-term follow-up. This was described as “an observation that reminds us that better treatments are still needed for patients with this chronically disabling disorder.”

Who funded the PACE trial?
The trial was funded by the Medical Research Council (MRC), the Department of Health, the Department of Work and Pensions and the Scottish Chief Scientist Office.

Would there have been any conflicts of interest, for example, the investigators’ past involvement in insurance companies?
No insurance company was involved in any aspect of the trial. There were some 19 investigators, three of whom had done consultancy work at various times for insurance companies. This consultancy work was not related to the conduct of the research. Furthermore, it is not clear how this would be a conflict of interest; other than, the interest shared by patients and health services in finding a treatment that helps patients.

Following the trend to report all interests, whether judged to be conflicting or not, all sources of income were listed as potential conflicts of interest in the relevant papers.

The patient information sheet informed all potential participants as to which organisations had funded the research, which is consistent with ethical guidelines.

Publications

Responses to Criticism

In the last few years, there have been many published criticisms of the PACE trial. Here are the main ones, and our published responses to each of them in turn. A full response to the criticisms made of the trial can be found in the many “frequently asked questions”, found elsewhere on this website.

Geraghty, Keith J. "‘PACE-Gate’: When clinical trial evidence meets open data access." J Health Psychol. 2017 Aug;22(9):1106-1112. https://journals.sagepub.com/doi/full/10.1177/1359105316675213

White PD, Chalder T, Sharpe M, Angus BJ, Baber HL, Bavinton J, Burgess M, Clark LV, Cox DL, DeCesare JC, Goldsmith KA. Response to the editorial by Dr Geraghty. Journal of Health Psychology. 2017 Aug;22(9):1113-7. https://journals.sagepub.com/doi/10.1177/1359105316688953?icid=int.sj-related-articles.citing-articles.20

Wilshire C, Kindlon T, Matthees A, McGrath S. Can patients with chronic fatigue syndrome really recover after graded exercise or cognitive behavioural therapy? A critical commentary and preliminary re-analysis of the PACE trial. Fatigue: Biomedicine, Health & Behavior. 2017 Jan 2;5(1):43-56. https://www.tandfonline.com/doi/full/10.1080/21641846.2017.1259724

Sharpe M, Chalder T, Johnson AL, Goldsmith KA, White PD. Do more people recover from chronic fatigue syndrome with cognitive behaviour therapy or graded exercise therapy than with other treatments?. Fatigue: Biomedicine, Health & Behavior. 2017 Jan 2;5(1):57-61. https://www.tandfonline.com/doi/abs/10.1080/21641846.2017.1288629

Wilshire CE, Kindlon T, Courtney R, Matthees A, Tuller D, Geraghty K, Levin B. Rethinking the treatment of chronic fatigue syndrome—a reanalysis and evaluation of findings from a recent major trial of graded exercise and CBT. BMC psychology. 2018 Dec;6(1):6. https://bmcpsychology.biomedcentral.com/articles/10.1186/s40359-018-0218-3

Sharpe M, Goldsmith K, Chalder T. The PACE trial of treatments for chronic fatigue syndrome: a response to WILSHIRE et al. BMC psychology. 2019 Dec;7(1):15. https://bmcpsychology.biomedcentral.com/articles/10.1186/s40359-019-0288-x

Further papers published using data from the PACE trial:

King E, Beynon M, Chalder T, Sharpe M, White PD. Patterns of daytime physical activity in patients with chronic fatigue syndrome. Journal of Psychosomatic Research 2020; 135: 110154. https://www.sciencedirect.com/science/article/abs/pii/S0022399919310323

Sharpe M, Goldsmith KA, Johnson AL, Chalder T, Walker J, White PD. Patient reaction to the PACE trial–Authors' reply. The Lancet Psychiatry. 2016 Feb 1;3(2):e8-9. https://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(16)00018-3/fulltext

Williams TE, Chalder T, Sharpe M, White PD. Heterogeneity in chronic fatigue syndrome–empirically defined subgroups from the PACE trial. Psychological medicine. 2017 Jun;47(8):1454-65. https://www.cambridge.org/core/journals/psychological-medicine/article/heterogeneity-in-chronic-fatigue-syndrome-empirically-defined-subgroups-from-the-pace-trial/4CB7DD589F3B23240A11131C8E8E2046

Lawn T, Kumar P, Knight B, Sharpe M, White PD. Psychiatric misdiagnoses in patients with chronic fatigue syndrome.  JRSM Short Reports 2010; 1(4):28.

Cella M, Sharpe M, Chalder T. Measuring disability in patients with chronic fatigue syndrome: reliability and validity of the Work and Social Adjustment Scale. Journal Psychosomatic Research 2011; 71:124-8.

Cella M, White PD, Sharpe M, Chalder T. Cognitions, behaviours and co-morbid psychiatric diagnoses in patients with chronic fatigue syndrome.  Psychological Medicine 2013; 43: 375–380

Cox DL, Burgess M, Chalder T, Sharpe M, White PD, Clark L. Training, supervision & therapists' adherence to manual based therapies. International Journal of Therapy and Rehabilitation 20(4):2013 April 2013

Dougall D, Johnson A, Goldsmith K, Sharpe M, Angus B, Chalder T, White PD. Adverse events and deterioration reported by participants in the PACE trial of therapies for chronic fatigue syndrome. Journal Psychosomatic Research 2014; 77: 20-26.

Sharpe M, Goldsmith KA, Johnson AL, Chalder T, Walker J, White PD. Rehabilitative treatments for chronic fatigue syndrome: long-term follow-up from the PACE trial. Lancet Psychiatry 2015; 2: 1067–74.

Lewith G, Stuart B, Chalder T, McDermott C, White PD. Complementary and alternative healthcare use by participants in the PACE trial of treatments for chronic fatigue syndrome. Journal Psychosomatic Research 2016; 87: 37–42.

Goldsmith KA, , Chalder T, White PD, Sharpe M, Pickles A. Measurement error, time lag, unmeasured confounding: Considerations for longitudinal estimation of the effect of a mediator in randomised clinical trials. Statistical Methods in Medical Research 2016 Sep 19.

July 2015 update: Analysis of mediators paper published
http://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(14)00069-8/abstract

Other papers recently published include:

The statistical plan for the trial:
http://www.biomedcentral.com/content/pdf/1745-6215-14-386.pdf
Recovery as an outcome:
http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=8988741&fileId=S0033291713000020
Pain as an outcome:
http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=9215309&fileId=S0033291713002201
How we did the trial:
http://pb.rcpsych.org/content/39/1/24.short

Here is a paper that describes an independent Cochrane review of exercise therapy in CFS, which included the PACE trial:
http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD003200.pub3/epdf/standard

21 September 2012 update: Health economics paper, including cost-effectiveness comparisons, has now been published in PLOS ONE, and is available for free download at this link.

11 March 2011 update: Full PACE paper and web appendix now available to download free of charge, after registering with The Lancet

Centre for Cancer Prevention

Funding Body:  Cancer Research UK

Principal Investigator:  Dr. Adam Brentnall, Prof. Giovanni Montana,

Overview

Breast density

Breast density (also known as mammographic density) is the amount of white and bright regions seen on a mammogram. High breast density can make it harder for doctors to detect breast cancer on a screening mammogram and also increases the risk of developing breast cancer.

Measuring breast density can become a useful health tool for women, however, the way it is measured still needs to be improved, and it is not clear how best to use the information to aid early detection and prevention of the disease.

Part of this project is framed in this context. We aim at finding more reliable ways of measuring breast density, and at evaluating the risk of not seeing cancer during the screening because of breast density.

Artificial intelligence (AI) in healthcare

The main ingredient of our project is developing AI algorithms to improve the risk assessment of breast cancer. With the increasing availability of medical data, AI has become an evolving trend in the medical field. In preventive health care, the wealth of available data provides opportunities for more accurate health monitoring. The social impact of using AI in healthcare is a complex matter that attracted the attention of governments, media, and society in general.

The project

Our project will develop an artificial intelligence system to design a risk-adapted screening programme, by assessing risk of breast cancer in a mammogram at screening, and the long-term risk of breast cancer following a negative screen by mammography.
The three questions we hope to answer are:

  • Can we improve the way we detect cancer in a mammogram at screening? How do we assess the risk?
  • Some women have very dense breasts, and this makes it difficult to spot the signs of breast cancer in the mammogram. A ``false negative'' is when a women is assessed as being at low risk for breast cancer, when in fact she is at high risk. How can we tell when a woman might be at risk of getting a false negative during a standard mammogram, and should be offered an alternative screening method?
  • What is the long-term risk of breast cancer following a negative screen by mammography? Who should we screen for breast cancer, and how often should screenings take place?

Further Information

Patient and Public Involvement group

The ultimate user of medical AI are patients. Thus the healthy development of AI in healthcare depends, to a certain extent, on researchers being able to understand the public’s views and communicate transparently about their research. This is why it is important to us to discuss with a PPI group about the best ways to communicate about complex artificial intelligence algorithms, and about the inclusion of a component based on artificial intelligence in long-term risk of breast cancer. 

Health and Lifestyle Research Unit

Principal Investigator:  Dr Katie Myers Smith,

If you are interested in taking part please click to email us: vapeline@qmul.ac.uk

 

Thank you for your interest in this new study looking at whether face-to-face support is important to help smokers quit when using an e-cigarette or whether the advice can be provided on the phone and via support messages (e.g. email).

The study is run by the Health and Lifestyle Research Unit at Wolfson Institute of Preventive Medicine, Queen Mary University of London and is funded by the National Institute for Health Research - Health Technology Assessment (NIHR-HTA).

Further details can be found in the Participant Information Sheet 

 

If you are interested in taking part please click to email us: vapeline@qmul.ac.uk

 

This study has been reviewed and approvedby the NRES Committee South West – Central Bristol Research Ethics Committee (20/SW/0179).